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Intra-articular ankle fracture (IAF) often leads to post-traumatic osteoarthritis (PTOA), resulting in significant long-term morbidity. While previous research has focused on the inflammatory cytokines and matrix metalloproteinases within the synovial fluid fracture hematoma (SFFH), the immune cell populations within SFFH that contribute to PTOA development remain underexplored. This study aimed to characterize the immune cell populations in SFFH to better understand their role in the inflammatory response and potential for inducing lasting cartilage damage. Twenty-four patients with IAF underwent surgical ankle aspiration to collect SFFH, which was analyzed using polychromatic flow cytometry. The analysis revealed that 72.8% of the CD45+ cells were lymphocytes, predominantly CD3+ T cells (76.5%), with 42.1% being CD4+ and 39.2% CD8+ T cells. Additionally, monocytes accounted for 21.2% of CD45+ cells, with small populations of natural killer cells and myeloid-derived suppressor cells also present. These findings emphasize the predominance of T cells, particularly CD4+ subsets, in the immune response following IAF. Understanding these dynamics is essential for developing targeted interventions to prevent PTOA. Future research should focus on elucidating the specific roles of these immune cell populations in PTOA progression and exploring potential therapeutic strategies. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To probe into the effects of Yangzheng Touxie Qudu method combined with NAC regimen (docetaxel + epirubicin + cyclophosphamide) chemotherapy on efficacy, T cell subsets and cancer-related fatigue in patients with triple negative breast cancer. METHODS: From Jun. 2022 to Jun. 2023, totally 100 cases of triple negative breast cancer diagnosed and treated in the hospital were extracted to be divided into the control group and observation group according to the random number table method, with 50 cases in each group. The control group was treated with NAC regimen, while the observation group received self formulated Yangzheng Touxie Qudu formula combined with NAC regimen. The efficacy, T-lymphocyte subsets, inflammatory factors, cancer-related fatigue levels, and incidence of adverse drug reactions of two groups were observed. RESULTS: The total effective rate of observation group was 82. 00% (41/50), significantly higher than that 58. 00% (29/50) of control group, the difference was statistically significant (P < 0. 05). Compared with before treatment, CD3+, CD4+, CD4+ / CD8+, interleukin (IL)-12 and IL-2 levels increased significantly in both groups after treatment, and the observation group was higher than the control group; compared with before treatment, CD8+, tumor necrosis factor-α, soluble interleukin-2 receptor levels, physical, cognitive and emotional fatigue scores decreased in both groups after treatment, and the observation group was lower than the control group, with statistically significant differences (P <0.05). The incidence of adverse drug reactions in observation group and control group was respectively 24.00% (12/50) and 28.00% (14/50), with no statistically significant difference (P>0.05). CONCLUSIONS: Yangzheng Touxie Qudu method combined with NAC regimen in the treatment of patients with triple negative breast cancer can significantly improve the efficacy and T cell subsets levels, reduce inflammatory reactions, and improve cancer-related fatigue with higher safety. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B virus (HBV) infection is a significant global public health concern, and the clearance of HBV is closely linked to the activity of HBV‐specific T cells, which is regulated by various co‐suppressor molecules. Cytotoxic T lymphocyte‐associated antigen 4 (CTLA‐4) is among these co‐suppressor molecules which induces T cell exhaustion by competitively inhibiting CD28 and dampening the function of HBV‐specific T cells. CTLA‐4 also plays a role in the regulation of T helper (Th) cell differentiation and influences cytokine release. In addition, CTLA‐4 can impact glucose metabolism in hepatocellular carcinoma through its interaction with T regulatory (Treg) cells. This review aims to provide a comprehensive overview of the existing literature related to the role of CTLA‐4 in HBV patients across different subsets of T cells. Additionally, we propose a discussion on the possible mechanisms through which CTLA‐4 may contribute to HBV infection, as well as the development of HBV‐induced cirrhosis and hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Background: Many research laboratories have long-term repositories of cryopreserved peripheral blood mononuclear cells (PBMC), which are costly to maintain but are of uncertain utility for immunological studies after decades in storage. This study investigated preservation of cell surface phenotypes and invitro functional capacity of PBMC from viraemic HIV+ patients and healthy seronegative control subjects, after more than 20 years of cryopreservation. Methods: PBMC were assessed by 18-colour flow cytometry for major lymphocyte subsets within T, B, NK, and dendritic cells and monocytes. Markers of T-cell differentiation and activation were compared with original immunophenotyping performed in 1995/1996 on fresh blood at the time of collection. Functionality of PBMC was assessed by culture with influenza antigen or polyclonal T-cell activation, to measure upregulation of activation-induced CD25 and CD134 (OX40) on CD4 T cells and cytokine production at day 2, and proliferative CD25+ CD4 blasts at day 7. RNA was extracted from cultures containing proliferating CD4+ blast cells, and intracellular HIV RNA was measured using short amplicons for both the Double R and pol region pi code assays, whereas long 4-kbp amplicons were sequenced. Results: All major lymphocyte and T-cell subpopulations were conserved after long-term cryostorage, except for decreased proportions of activated CD38+HLA-DR+ CD4 and CD8 T cells in PBMC from HIV+ patients. Otherwise, differences in T-cell subpopulations between recent and long-term cryopreserved PBMC primarily reflected donor age-associated or HIV infectionassociated effects on phenotypes. Proportions of naïve, memory, and effector subsets of T cells from thawed PBMC correlated with results from the original flow cytometric analysis of respective fresh blood samples. Antigen-specific and polyclonal T-cell responses were readily detected in cryopreserved PBMC from HIV+ patients and healthy control donors. Intracellular HIV RNA quantitation by pi code assay correlated with original plasma viral RNA load results. Full-length intracellular and supernatant-derived amplicons were generated from 5/12 donors, and sequences were ≥80% wild-type, consistent with replication competence. Conclusions: This unique study provides strong rationale and validity for using well-maintained biorepositories to support immunovirological research even decades after collection. [ABSTRACT FROM AUTHOR]

Objectives: Diabetic retinopathy (DR) is a prevalent microvascular complication in diabetic patients. Various mechanisms have been implicated in the pathogenesis of DR. Previous studies have observed the relationship between immune factors and DR, but the causal relationship has not been determined. Methods: We conducted a two-sample Mendelian randomization (MR) analysis of 731 immune cells and DR, using publicly available genome-wide association study (GWAS) summary statistics, to evaluate potential causal relationships between them. Four types of immune traits were included in the analysis through flow cytometry. GWAS statistics for DR were obtained from the Finngen database, which performed GWAS on 190,594 European individuals (Ncase = 14,584, Ncontrol = 176,010) to assess genetically predicted DR. The primary method used to perform causality analysis was inverse variance weighting (IVW). Results: Following false discovery rate (FDR) correction, 11MFI-DR, 5AC-DR, 5RC-DR, and 1MP-DR reached a significant causal association level (PFDR < 0.05). Notably, all AC traits exhibited potential associations with a decreased risk of DR(OR < 1), while a majority of MFI traits, along with the singular MP trait, exhibited potential associations with an increased risk of DR (OR > 1). The highest proportion of T-cell subsets in the final results. Conclusion: This study elucidates that the progression of DR is intricately influenced by immune responses, thereby confirming the immunological susceptibility of DR. Our findings may offer new targets for diagnosing and treating DR, as well as aid in developing therapeutic strategies from an immunological standpoint. [ABSTRACT FROM AUTHOR]

Introduction: The gut microbiota, T cell subsets, and cytokines participate in tuberculosis (TB) pathogenesis. To date, the mechanisms by which these factors interactively promote TB development at different time points remain largely unclear. In the context of this study, We looked into the microorganisms in the digestive tract, T cell types, and cytokines related to tuberculosis. Methods: According to QIIME2, we analyzed 16SrDNA sequencing of the gut microbiome on the Illumina MiSeq. Enzyme-linked immunosorbent assay was used to measure the concentrations of cytokines. Results: We showed the presence of 26 identifiable differential microbiomes in the gut and 44 metabolic pathways between healthy controls and the different time points in the development of TB in patients. Five bacterial genera (Bacteroides, Bifidobacterium, Faecalibacterium, Collinsella, and Clostridium) were most closely associated with CD4/CD8, whereas three bacterial taxa (Faecalibacterium, Collinsella, and Clostridium) were most closely associated with CD4. Three bacterial taxa (Faecalibacterium, Ruminococcus, and Dorea) were most closely associated with IL-4. Ruminococcus was most closely associated with IL-2 and IL-10. Conclusion: Diverse microorganisms, subsets of T cells, and cytokines, exhibiting varying relative abundances and structural compositions, were observed in both healthy controls and patients throughout distinct phases of tuberculosis. Gaining insight into the function of the gut microbiome, T cell subsets, and cytokines may help modulate therapeutic strategies for TB. [ABSTRACT FROM AUTHOR]

[Objectives]This study aimed to investigate the effect of Armadillo/β-catenin like repeat containing protein(EmARM-β), a Th1 cytokine stimulatory molecule from Eimeria maxima on functions of chicken immune-related cells. [Methods]In this study, chicken peripheral blood mononuclear cell(PBMC), CD8+T cells, and CD4+CD25-T cells were isolated by density gradient cell centrifugation method and immunomagnetic bead sorting method, respectively. Subsequently, EmARM-β recombinant protein(rEmARM-β)was incubated with the above cells in vitro, CCK-8 solution and qPCR were used to detect and analyze the effects on the proliferation ability of the above cells and the secretion levels of cytokines, respectively. [Results]The results showed that purity of chicken CD8+T cells and CD4+CD25-T cells were 93.01% and 88.88%, respectively. rEmARM-β significantly enhanced the proliferation capacity, upregulated Th1 type cytokines(ifn-γ, and il-2)and proinflammatory cytokines(il-1β, il-6, and il-17a)mRNA levels in chicken PBMC compared with the control group. Effective stimulations of rEmARM-β on the cell proliferation capacity and mRNA levels of ifn-γ, il-2, tnf-α, perforin, fasl, and fas in chicken CD8+T cells were also observed. The molecule significantly promoted cell proliferation capacity, upregulated the mRNA levels of ifn-γ and il-2, and downregulated the mRNA levels of il-4 and il-10 in chicken CD4+CD25-T cells. [Conclusions]EmARM-β, the Th1 cytokine stimulatory molecule, could effectively promote cell proliferation, secretions of Th1 cytokines and proinflammatory cytokines of chicken PBMC and T cell subsets, suggesting the EmARM-β is the potential candidate antigen to develop novel vaccine against chicken coccidiosis. [ABSTRACT FROM AUTHOR]

γδ T cells, a specialized subset of T lymphocytes, have garnered significant attention within the realm of cancer immunotherapy. Operating at the nexus between adaptive and innate immunological paradigms, these cells showcase a profound tumor discernment repertoire, hinting at novel immunotherapeutic strategies. Significantly, these cells possess the capability to directly identify and eliminate tumor cells without reliance on HLA-antigen presentation. Furthermore, γδ T cells have the faculty to present tumor antigens to αβ T cells, amplifying their anti-tumoral efficacy.Within the diverse and heterogeneous subpopulations of γδ T cells, distinct immune functionalities emerge, manifesting either anti-tumor or pro-tumor roles within the tumor microenvironment. Grasping and strategically harnessing these heterogeneous γδ T cell cohorts is pivotal to their integration in tumor-specific immunotherapeutic modalities. The aim of this review is to describe the heterogeneity of the γδ T cell lineage and the functional plasticity it generates in the treatment of malignant tumors. This review endeavors to elucidate the intricate heterogeneity inherent to the γδ T cell lineage, the consequential functional dynamics in combating malignancies, the latest advancements from clinical trials, and the evolving landscape of γδ T cell-based oncological interventions, while addressing the challenges impeding the field. [ABSTRACT FROM AUTHOR]

Background: Patients with immunodeficiencies commonly experience diagnostic delays resulting in morbidity. There is an unmet need to identify patients earlier, especially those with high risk for complications. Compared to immunoglobulin quantification and flowcytometric B cell subset analysis, expanded T cell subset analysis is rarely performed in the initial evaluation of patients with suspected immunodeficiency. The simultaneous interpretation of multiple immune variables, including lymphocyte subsets, is challenging. Objective: To evaluate the diagnostic value of cluster analyses of immune variables in patients with suspected immunodeficiency. Methods: Retrospective analysis of 38 immune system variables, including seven B cell and sixteen T cell subpopulations, in 107 adult patients (73 with immunodeficiency, 34 without) evaluated at a tertiary outpatient immunology clinic. Correlation analyses of individual variables, k‐means cluster analysis with evaluation of the classification into "no immunodeficiency" versus "immunodeficiency" and visual analyses of hierarchical heatmaps were performed. Results: Binary classification of patients into groups with and without immunodeficiency was correct in 54% of cases with the full data set and increased to 69% and 75% of cases, respectively, when only 16 variables with moderate (p <.05) or 7 variables with strong evidence (p <.01) for a difference between groups were included. In a cluster heatmap with all patients but only moderately differing variables and a heatmap with only immunodeficient patients restricted to T cell variables alone, segregation of most patients with common variable immunodeficiency and combined immunodeficiency was observed. Conclusion: Cluster analyses of immune variables, including detailed lymphocyte flowcytometry with T cell subpopulations, may support clinical decision making for suspected immunodeficiency in daily practice. [ABSTRACT FROM AUTHOR]

Autosomal dominant polycystic kidney disease (ADPKD) has cancer-like pathophysiology. In this study, we aimed to investigate the phenotype of peripheral blood (PB) T cell subsets and immune checkpoint inhibitor expression of ADPKD patients across different chronic kidney disease (CKD) stages. Seventy-two patients with ADPKD and twenty-three healthy controls were included in the study. The patients were grouped into five different CKD stages, according to glomerular filtration rate (GFR). PB mononuclear cells were isolated and T cell subsets and cytokine production were examined by flow cytometry. CRP levels, height-adjusted total kidney volume (htTKV), rate of hypertension (HT) differed significantly across different GFR stages in ADPKD. T cell phenotyping revealed significantly elevated CD3+ T cells, CD4+, CD8+, double-negative, and double-positive subsets and significantly elevated IFN-γ and TNF-α producing subsets of CD4+, CD8+ cells. The expression of checkpoint inhibitors CTLA-4, PD-1, and TIGIT by T cell subsets was also increased to various extent. Additionally, Treg cell numbers and suppressive markers CTLA-4, PD-1, and TIGIT were significantly elevated in ADPKD patients' PB. Treg CTLA4 expression and CD4CD8DP T cell frequency in patients with HT were significantly higher. Lastly, HT and increased htTKV and higher frequency of PD1+ CD8SP were found to be risk factors for rapid disease progression. Our data provide the first detailed analyses of checkpoint inhibitor expression by PB T cell subsets during stages of ADPKD, and that a higher frequency of PD1+ CD8SP cells is associated with rapid disease progression. [ABSTRACT FROM AUTHOR]

Currently, multiple studies have indicated that CD8+ T lymphocytes play a role in causing damage to the exocrine glands through acinar injury in primary Sjögren's syndrome (pSS). The aim of this research was to assess the imbalance of circulating CD8+ T cell subsets. We analyzed blood samples from 34 pSS patients and 34 healthy individuals as controls. We used flow cytometry to enumerate CD8+ T cell maturation stages, using as markers CD62L, CD28, CD27, CD4, CD8, CD3, CD45RA and CD45. For immunophenotyping of 'polarized' CD8+ T cell subsets, we used the following monoclonal antibodies: CXCR5, CCR6, CXCR3 and CCR4. The findings revealed that both the relative and absolute numbers of 'naïve' CD8+ T cells were higher in pSS patients compared to the healthy volunteers. Conversely, the proportions of effector memory CD8+ T cells were notably lower. Furthermore, our data suggested that among patients with pSS, the levels of cytotoxic Tc1 CD8+ T cells were reduced, while the frequencies of regulatory cytokine-producing Tc2 and Tc17 CD8+ T cells were significantly elevated. Simultaneously, the Tc1 cell subsets displayed a negative correlation with immunoglobulin G, rheumatoid factor, the Schirmer test and unstimulated saliva flow. On the other hand, the Tc2 cell subsets exhibited a positive correlation with these parameters. In summary, our study indicated that immune dysfunction within CD8+ T cells, including alterations in Tc1 cells, plays a significant role in the development of pSS. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical efficacy of TCM Buwu decoction combined with phototherapy in the treatment of advanced vitiligo, and to detect the changes of heme oxygenase-1（ HO-1） level, T cell subpopulation, nuclear factor E2-related transcription factor 2（Nrf2） and dead bone tablet 1（p62） mRNA in peripheral blood of patients before and after treatment, so as to explore the preliminary mechanism of action. Methods: According to the inclusion criteria of advanced vitiligo patients, sixty patients were selected and randomly divided into obesevation group （30 cases） and control group（30 cases）. Both groups were treated with 308 excimer light, and the observation group was treated with Buwu decoction on the basis of phototherapy. The clinical efficacy of the two groups was evaluated, and the level of HO-1 in serum was detected by ELISA; T cell subsets of peripheral blood lymphocytes were detected by flow cytometry; the expressions of Nrf2 and p62 mRNA in PBMC were detected by RT-qPCR. Results: There was significant difference in clinical efficacy between the two groups（ Z=0.019, P<0.05）. The level of HO-1 in peripheral blood of 2 groups after treatment was significantly higher than that before treatment （P<0.01）. After treatment, the proportion of peripheral blood lymphocytes CD3+CD8+T cells was lower than before treatment, and the proportion of CD4+/CD8+ was significantly higher than before treatment （P< 0.01）. The relative expression levels of Nrf2 and p62 mRNA in peripheral blood lymphocytes of two groups were higher after treatment than before treatment （P<0.01）. Conclusion: TCM combined with 308 excimer light can effectively treat advanced vitiligo, and can up-regulate Nrf2 and p62 mRNA to promote the expression of HO-1 in its downstream, thus playing antioxidant, anti-inflammatory and immune regulation roles, and reduce the proportion of CD3+CD8+T cells in peripheral blood, whose effect is better than that of simple light therapy group. [ABSTRACT FROM AUTHOR]

The thymus gland is a central lymphoid organ in which developing T cell precursors, known as thymocytes, undergo differentiation into distinct type of mature T cells, ultimately migrating to the periphery where they exert specialized effector functions and orchestrate the immune responses against tumor cells, pathogens and selfantigens. The mechanisms supporting intrathymic T cell differentiation are pleiotropically regulated by thymic peptide hormones and cytokines produced by stromal cells in the thymic microenvironment and developing thymocytes. Interestingly, in the same way as T cells, thymic hormones (herein exemplified by thymosin, thymulin and thymopoietin), can circulate to impact immune cells and other cellular components in the periphery. Evidence on how thymic function influences tumor cell biology and response of patients with cancer to therapies remains unsatisfactory, although there has been some improvement in the knowledge provided by recent studies. Herein, we summarize research progression in the field of thymus-mediated immunoendocrine control of cancer, providing insights into how manipulation of the thymic microenvironment can influence treatment outcomes, including clinical responses and adverse effects of therapies. We review data obtained from clinical and preclinical cancer research to evidence the complexity of immunoendocrine interactions underpinning anti-tumor immunity. [ABSTRACT FROM AUTHOR]

This multiplex staining panel was developed to differentiate cattle T cells into conventional (CD4 and CD8) and unconventional (γδ‐TCR) subsets as well as their stage of differentiation and activation. The combination of CD45RO and CD62L allows the identification of naïve (TNaïve), central memory (TCM), effector memory (TEM) and terminal effector (TTE) T cells. Activated cattle T cells (TAV) can be identified by the cell surface expression of CD25. This panel was developed using cryopreserved cattle peripheral blood mononuclear cells (PBMCs) and tested on fresh as well as stimulated PBMCs. Therefore, this 8‐color, 10‐parameter flow cytometry panel simultaneously identifies cattle TNaïve, TAV, TCM, TEM, TTE and γδ‐TCR cells. This panel will improve our ability to examine T‐cell response to pathogens and vaccines in cattle including the potential to identify previously undescribed subpopulations. Furthermore, this panel can be readily optimized for other bovid species as many of these reagents are likely to cross react. [ABSTRACT FROM AUTHOR]

T lymphocytes, as a vital component of the adaptive immune system, play a crucial role in maintaining immune health. A thorough investigation of their maturation and aging processes is essential for achieving a comprehensive understanding of the immune system. In this review, we provide an overview of the developmental trajectory of various T cell subsets, encompassing not only the well-known naive, effector, memory subgroups and regulatory T cells, but also delving deeper into unconventional and distinct subgroups such as γδ T cells, mucosal-associated invariant T (MAIT) cells, and natural killer T (NKT) cells. We place particular emphasis on the myriad transformations these cells undergo during the aging process.The advent of single-cell technology in recent years has significantly advanced our understanding of the fundamental mechanisms underlying T cell development and aging. In conclusion, we highlight potential avenues for addressing the persistent challenges encountered in T cell maturation and aging research.

Background: Selective IgA deficiency (SIgAD) is the most prevalent inborn errors of immunity with almost unknown etiology. This study aimed to investigate the clinical diagnostic and prognostic values of lymphocyte subsets and function in symptomatic SIgAD patients. Methods: A total of 30 available SIgAD patients from the Iranian registry and 30 age-sex-matched healthy controls were included in the present study. We analyzed B and T cell peripheral subsets and T cell proliferation assay by flow cytometry in SIgAD patients with mild and severe clinical phenotypes. Results: Our results indicated a significant increase in naïve and transitional B cells and a strong decrease in marginal zone-like and switched memory B-cells in SIgAD patients. We found that naïve and central memory CD4+ T cell subsets, as well as Th1, Th2 and regulatory T cells, have significantly decreased. On the other hand, there was a significant reduction in central and effector memory CD8+ T cell subsets, whereas proportions of both (CD4+ and CD8+) terminally differentiated effector memory T cells (TEMRA) were significantly elevated in our patients. Although some T cell subsets in severe SIgAD were similar, a decrease in marginal-zone and switched memory B cells and an increase in CD21low B cell of severe SIgAD patients were slightly prominent. Moreover, the proliferation activity of CD4+ T cells was strongly impaired in SIgAD patients with a severe phenotype. Conclusion: SIgAD patients have varied cellular and humoral deficiencies. Therefore, T cell and B cell assessment might help in better understanding the heterogeneous pathogenesis and prognosis estimation of the disease. [ABSTRACT FROM AUTHOR]

The HIV-1 reservoirs harbor the latent proviruses that are integrated into the host genome. It is a challenging task to eradicate the proviruses in order to achieve an HIV cure. We have described a strategy for the clearance of HIV-1 infection through selective elimination of host cells harboring replication-competent HIV (SECH), by inhibition of autophagy and promotion of apoptosis during viral reactivation. HIV-1 can infect various CD4+ T cell subsets, but it is not known whether the SECH approach is equally effective in targeting HIV-1 reservoirs in these different subsets in vivo. In a humanized mouse model, we found that treatments of HIV-1 infection by suppressive antiretroviral therapy (ART) led to the establishment of latent HIV reservoirs in naïve, central memory and effector memory T cells. Moreover, SECH treatments could clear latent HIV-1 reservoirs in these different T cell subsets of humanized mice. Co-culture studies showed that T cell subsets latently infected by HIV-1, but not uninfected bystander cells, were susceptible to cell death induced by SECH treatments. Our study suggests that the SECH strategy is effective for specific targeting of latent HIV-1 reservoirs in different T cell subsets. [ABSTRACT FROM AUTHOR]

Background: Immunological phenotypes and differentiation statuses commonly decide the T cell function and anti-tumor ability. However, little is known about these alterations in CML patients. Method: Here, we investigated the immunologic phenotypes (CD38/CD69/HLADR/CD28/CD57/BTLA/TIGIT/PD-1) of T subsets (TN, TCM, TEM, and TEMRA) in peripheral blood (PB) and bone marrow (BM) from de novo CML patients (DNCML), patients who achieved a molecular response (MR) and those who failed to achieve an MR (TKI-F) after tyrosine kinase inhibitor (TKI) treatment using multicolor flow cytometry. Results: CD38 or HLA-DR positive PB CD8+TN and TCM cells decreased in the DN-CML patients and this was further decreased in TKI-F patients. Meanwhile, the level of PD-1 elevated in CD8+ TEM and TEMRA cells from PB in all groups. Among BM sample, the level of HLA-DR+CD8+TCM cells significantly decreased in all groups and CD8+TEMRA cells from TKI-F patients exhibited increased level of TIGIT and CD8+ tissue-residual T cells (TRM) from DN-CML patients expressed a higher level of PD-1 and TIGIT. Lastly, we found a significantly decreased proportion of CD86+ dendritic cells (DCs) and an imbalanced CD80/CD86 in the PB and BM of DN-CML patients, which may impair the activation of T cells. Conclusion: In summary, early differentiated TN and TCM cells from CML patients may remain in an inadequate activation state, particularly for TKI-F patients. And effector T cells (TEM, TEMRA and TRM) may be dysfunctional due to the expression of PD-1 and TIGIT in CML patients. Meanwhile, DCs cells exhibited the impairment of costimulatory molecule expression in DN-CML patients. Those factors may jointly contribute to the immune escape in CML patients. [ABSTRACT FROM AUTHOR]

The pandemic coronavirus disease 2019 (COVID-19) is a major global public health concern and several protective vaccines, or preventive/therapeutic approaches have been developed. Sinovac-CoronaVac, an inactivated whole virus vaccine, can protect against severe COVID-19 disease and hospitalization, but less is known whether it elicits long-term T cell responses and provides prolonged protection. This is a longitudinal surveillance study of SARS-CoV-2 receptor binding domain (RBD)-specific IgG levels, neutralizing antibody levels (NAb), T cell subsets and activation, and memory B cells of 335 participants who received two doses of CoronaVac. SARS-CoV-2 RBD-specific IgG levels were measured by enzyme-linked immunosorbent assay (ELISA), while NAb were measured against two strains of SARS-CoV-2, the Wuhan and Delta variants. Activated T cells and subsets were identified by flow cytometry. Memory B and T cells were evaluated by enzyme-linked immune absorbent spot (ELISpot). Two doses of CoronaVac elicited serum anti-RBD antibody response, elevated B cells with NAb capacity and CD4+ T cell-, but not CD8+ T cell-responses. Among the CD4+ T cells, CoronaVac activated mainly Th2 (CD4+ T) cells. Serum antibody levels significantly declined three months after the second dose. CoronaVac mainly activated B cells but T cells, especially Th1 cells, were poorly activated. Activated T cells were mainly Th2 biased, demonstrating development of effector B cells but not long-lasting memory plasma cells. Taken together, these results suggest that protection with CoronaVac is short-lived and that a third booster dose of vaccine may improve protection. [ABSTRACT FROM AUTHOR]

COVID-19 is being extensively studied, and much remains unknown regarding the long-term consequences of the disease on immune cells. The different arms of the immune system are interlinked, with humoral responses and the production of high-affinity antibodies being largely dependent on T cell immunity. Here, we longitudinally explored the effect COVID-19 has on T cell populations and the virus-specific T cells, as well as neutralizing antibody responses, for 6-7 months following hospitalization. The CD8+ TEMRA and exhausted CD57+ CD8+ T cells were markedly affected with elevated levels that lasted long into convalescence. Further, markers associated with T cell activation were upregulated at inclusion, and in the case of CD69+ CD4+ T cells this lasted all through the study duration. The levels of T cells expressing negative immune checkpoint molecules were increased in COVID-19 patients and sustained for a prolonged duration following recovery. Within 2-3 weeks after symptom onset, all COVID-19 patients developed anti-nucleocapsid IgG and spike-neutralizing IgG as well as SARS-CoV-2-specific T cell responses. In addition, we found alterations in follicular T helper (TFH) cell populations, such as enhanced TFH-TH2 following recovery from COVID-19. Our study revealed significant and long-term alterations in T cell populations and key events associated with COVID-19 pathogenesis. [ABSTRACT FROM AUTHOR]

Common variable immunodeficiency (CVID) is a heterogeneous group of inborn errors of immunity characterized by reduced serum concentrations of different immunoglobulin isotypes. CVID is the most prevalent symptomatic antibody deficiency with a broad range of infectious and non-infectious clinical manifestations. Various genetic and immunological defects are known to be involved in the pathogenesis of CVID. Monogenic defects account for the pathogenesis of about 20-50% of CVID patients, while a variety of cases do not have a defined genetic background. Deficiencies in molecules of B cell receptor signaling or other pathways involving B-cell development, activation, and proliferation could be associated with monogenetic defects of CVID. Genetic defects damping different B cell developmental stages can alter B- and even other lymphocytes' differentiation and might be involved in the clinical and immunologic presentations of the disorder. Reports concerning T and B cell abnormalities have been published in CVID patients, but such comprehensive data on monogenic CVID patients is few and no review article exists to describe the abrogation of lymphocyte subsets in these disorders. Hence, we aimed to review the role of altered B- and T-cell differentiation in the pathogenesis of CVID patients with monogenic defects. [ABSTRACT FROM AUTHOR]

The purpose of the experiment was to study the effect of lavender hydrosol on immune indexes of Xinjiang brown cattle. 48 Xinjiang brown cattle were randomly divided into four groups: Control group, 0.5% lavender hydrosol group, 1.0% lavender hydrosol group and 1.5% lavender hydrosol group. Blood was collected on the 40th day of the experiment, and some indexes such as immunoglobulin, cytokines, complement and T cell subsets in serum were measured. The results showed that compared with the control group, the serum sCD4 content and sCD4/sCD8 ratio of lavender hydrosol test group were extremly increased (P<0.01). The content of IgA and C3 in serum samples of 0.5% group were significantly increased (P<0.05). The content of IgA, IL-10 and C3 in 1.0% group were extremely increased (P<0.01), and the content of IgG, IgM, IL-2, IL-4 and C4 were significantly increased (P<0.05). IgA content in 1.5% group was extremely increased (P<0.01), IgG, IL-2, IFN-γ and C4 content were significantly increased (P<0.05). The experiment indicates that lavender hydrosol can significantly or extremely significantly improve the immune capacity of Xinjiang brown cattle, and 1.0% lavender hydrosol is recommended for the best effect. [ABSTRACT FROM AUTHOR]

Objective: To study the efficacy of tislelizumab combined with albumin paclitaxel in the treatment of advanced lung cancer, and to explore its effect on T cell subsets. Methods: 80 patients with advanced lung cancer who were treated in the hospital from July 2018 to October 2021 were selected and divided into monotherapy group and joint group according to different treatment methods, with 40 cases in each group. The monotherapy group received albumin paclitaxel treatment, and the joint group received tisleli beads combined with albumin. To compare the clinical efficacy, adverse reactions, serum IgA and IgG levels before and posttreatment, and peripheral blood CD4+ and CD8+ T cell subsets between the two groups of patients. Results: (1) The clinical treatment effective rate of patients in the joint group was 87.5 %, which was higher than the clinical treatment effective rate of 67.5 % in the monotherapy group (P<0.05); (2) Liver and kidney damage, vomiting, fatigue, and leukopenia in the two groups of patients posttreatment There was no difference in the incidence of adverse reactions such as neurotoxicity and hand-foot syndrome(P>0.05); (3) Serum IgA and IgG of patients in the joint group posttreatment were higher than those in the monotherapy group(P<0.05); (4) Study posttreatment, the ratio of CD4+ and CD4+ /CD8+ T lymphocytes in the group was higher than that of the monotherapy group (P<0.05), while the ratio of CD8+ T lymphocytes was lower than that of the monotherapy group (P<0.05). Conclusion: The treatment of tisleli beads combined with albumin paclitaxel can significantly improve the clinical treatment efficiency of patients with advanced lung cancer, but does not increase the incidence of adverse reactions, and can effectively improve the immune function of patients. [ABSTRACT FROM AUTHOR]

Simple Summary: T cell-based therapies can be costly, inconsistent, and differentially effective for patients. The limiting reagent for T cell-based immunotherapies is the T cell itself. T cell growth has been linked to endogenously delivered cytokines and messenger proteins that indicate the status of inflammation of the local system in the body. IL-2, IL-7, and IL-15 are the specific cytokines that have been identified in combination to deliver accelerated growth to different T cell subsets. This study focuses on the growth of T cell subsets subject to different combinations of IL-2, IL-7, and IL-15 in the experiment. Based on growth data, mathematical models were developed to project the optimal growth conditions for CD4+ and CD8+ Naïve and Memory T Cells. RNA sequence data is finally analyzed to study the gene networks that influence growth pathways, specifically for CD4+ and CD8+ naïve and memory subsets. The growth of T cells ex vivo for the purpose of T cell therapies is a rate-limiting step in the overall process for cancer patients to achieve remission. Growing T cells is a fiscally-, time-, and resource-intensive process. Cytokines have been shown to accelerate the growth of T cells, specifically IL-2, IL-7, and IL-15. Here a design of experiments was conducted to optimize the growth rate of different naïve and memory T cell subsets using combinations of cytokines. Mathematical models were developed to study the impact of IL-2, IL-7, and IL-15 on the growth of T cells. The results show that CD4+ and CD8+ naïve T cells grew effectively using moderate IL-2 and IL-7 in combination, and IL-7, respectively. CD4+ and CD8+ memory cells favored moderate IL-2 and IL-15 in combination and moderate IL-7 and IL-15 in combination, respectively. A statistically significant interaction was observed between IL-2 and IL-7 in the growth data of CD4+ naïve T cells, while the interaction between IL-7 and IL-15 was found for CD8+ naïve T cells. The important genes and related signaling pathways and metabolic reactions were identified from the RNA sequencing data for each of the four subsets stimulated by each of the three cytokines. This systematic investigation lays the groundwork for studying other T cell subsets. [ABSTRACT FROM AUTHOR]

The role of T cells in the control of SARS-CoV-2 infection has been underestimated in favor of neutralizing antibodies. However, cellular immunity is essential for long-term viral control and protection from disease severity. To understand T-cell immunity in the absence of antibody generation we focused on a group of SARS-CoV-2 Non-Seroconvertors (NSC) recovered from infection. We performed an immune comparative analysis of SARS-CoV-2 infected individuals stratified by the absence or presence of seroconversion and disease severity. We report high levels of total naïve and low effector CD8+ T cells in NSC. Moreover, reduced levels of T-cell activation monitored by PD-1 and activation-induced markers were observed in the context of functional SARS-CoV-2 T-cell responses. Longitudinal data indicate the stability of the NSC phenotype over three months of follow-up after infection. Together, these data characterized distinctive immunological traits in NSC including skewed cellular distribution, low activation and functional SARS-CoV-2 T-cell responses. This data highlights the value of T-cell immune monitoring in populations with low seroconversion rates in response to SARS-CoV-2 infection and vaccination. [ABSTRACT FROM AUTHOR]

Objective: To explore the effect of Xiaoer-feire-kechuan oral solution combined with recombinant human interferon α1b injections with spray inhalation on T cell subsets and inflammatory cytokines of children with respiratory syncytial virus pneumonia (RSVP). Methods: 105 cases of children with RSVP in our Hospital from July 2020 to July 2021 were selected. According to the random indicator method, they were divided into the control group (52 cases) and the observation group (53 cases). Children of the two groups were treated with conventional medicine, the control group were treated with recombinant human interferon α1b injections on this basis, the observation group were treated with Xiaoer-feire-kechuan oral solution combined with recombinant human interferon α1b injections with spray inhalation. The two groups were treated for 7 days. Clinical curative effect was evaluated after treatment. The general indexes of the two groups were compared. The peripheral blood levels of CD3+, CD4+, CD8+ and serum levels of Tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukin-6(IL-6) of the two groups before and after treatment were compared. The adverse reaction incidence of two groups of patients during treatment were observed. Results: The total clinical effective rate of the observation group was higher than that of the control group (P<0.05). The rhonchus disappearance time, hospital stay time, body temperature relapse time and cough reduction time of the observation group were significantly less than that of the control group(P<0.05). Compared with before treatment, the levels of CD3+ and CD4+ in peripheral blood increased, and the level of CD8+ in peripheral blood decreased in the two groups after treatment(P<0.05). After treatment, the levels of CD3+ and CD4+ in peripheral blood of the observation group were higher than those of the control group (P<0.05). The level of CD8+ in peripheral blood was lower than that in control group (P<0.05). The levels of serum TNF-α, CRP, IL-6 of the two groups after treatment were significantly lower than before treatment (P<0.05), and levels of serum TNF-α, IL-6, CRP of the observation group were lower than that of the control group (P<0.05). At the same time, the levels of TNF-α, CRP and IL-6 of the observation group were significantly lower than those of the control group (P<0.05). There was no difference in the incidence of adverse reactions between the two groups during treatment(x² =0.501, P=0.479). Conclusions: Xiaoer-feire-kechuan oral solution combined with recombinant human interferon α1b injections with spray inhalation has good clinical efficacy in the treatment of children with RSVP, which is helpful to control clinical symptoms, improve immune function, inhibit inflammatory response, and has good safety. [ABSTRACT FROM AUTHOR]

Objective: To observe the effect of Reduning injection combined with ganciclovir injection on serum inflammatory factors and T cell subsets in children with respiratory syncytial virus (RSV) infection pneumonia. Methods: 60 children with RSV pneumonia were selected who were treated in our hospital from January 2017 to December 2020, and they were randomly divided into control group and study group, 30 cases in each group. The control group was treated with ganciclovir injection, and the study group was treated with Reduning injection combined with ganciclovir injection for 7 d. The curative effect, serum inflammatory factors, T cell subsets, symptom relief time and adverse reactions were compared between the two groups. Results: The total effective rate of the study group was 93.33%, which was higher than 66.67% of the control group (P<0.05). After treatment, the expression levels of procalcitonin (PCT), C-reactive protein (CRP) and interleukin-6 (IL-6) in the study group were lower than those in the control group (P<0.05). After treatment, the expression level of CD8+ in the study group was lower than that in the control group, CD3+, CD4+, CD4+/ CD8+ in the study group were higher than those in the control group(P<0.05). The remission time of cough, dyspnea and wheezing in the study group was shorter than that in the control group(P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05). Conclusion: Reduning injection combined with ganciclovir injection is effective in the treatment of children with RSV infection pneumonia. It can effectively improve the clinical symptoms, reduce the level of serum inflammatory factors, improve the immune function of the body, and has good safety. [ABSTRACT FROM AUTHOR]

Objective: To observe the effects of dexmedetomidine combined with sufentanil for postoperative analgesia on T cell subsets, serum inflammatory factors and pain mediators in elderly patients with lung cancer. Methods: 200 cases patients who underwent radical resection of lung cancer in our hospital were selected from July 2017 to December 2020. According to the random digital table method, the patients were divided into study group（n=100） and control group（n=100）. The control group used sufentanil for postoperative analgesia, and the study group used dexmedetomidine combined with sufentanil for postoperative analgesia. Visual Analogue Scale（VAS） and Ramsay Sedation score, peripheral blood T cell subsets, serum inflammatory factors, pain mediators index and adverse reactions in the two groups were observed. Results: The Ramsay Sedation and VAS scores at 6 h, 12 h, 24 h and 48 h after operation in the two groups were lower than those at 1 h after operation（P<0.05）, the Ramsay Sedation scores was higher than that of the control group at the above time points, while the VAS score of the study group was lower than that of the control group（P<0.05）. The levels of serum interferon-γ（IFN-γ） and interleukin-6（IL-6） in the two groups at 24 h after operation increased, but the IFN-γ and IL-6 in the study group were lower than those in the control group 24 h after operation（P<0.05）. The CD8+increased and CD3+, CD4+,CD4+/CD8+decreased in the two groups at 24 h after operation（P<0.05）, but CD8+was lower than that of the control group, and the CD3+,CD4+, CD4+/CD8+in the study group were higher than those in the control group at 24 h after operation（P<0.05）. The levels of serum β-endorphin（β-EP）, substance P（SP） and nitric oxide（NO） were increased in the two groups at 24 h after operation, but the study group was lower than the control group（P<0.05）. There was no significant difference in the incidence of adverse reactions between the two groups（P>0.05）. Conclusion: Dexmedetomidine combined with sufentanil for postoperative analgesia in elderly patients with lung cancer has significant analgesic and sedative effect, and can reduce immunosuppression and inflammatory reaction, with high safety. [ABSTRACT FROM AUTHOR]

Aim: To characterize immune suppression in lymphoma, thymocyte selection‐associated high mobility group box protein (TOX) expression and co‐expression with programmed cell death receptor‐1 (PD‐1), T cell immunoglobulin mucin‐domain‐containing‐3 (Tim‐3), and CD244 in CD3+, CD4+, CD8+, and regulatory T (Treg) cells from patients with lymphomas were analyzed. Methods: TOX expression and co‐expression with PD‐1, Tim‐3, and CD244 in CD3+, CD4+, Treg, and CD8+ T cells were analyzed by multi‐color fluorescent flow cytometry using peripheral blood (PB) from 13 newly diagnosed, untreated lymphoma patients, and 11 healthy individuals. Results: An increased percentage of TOX+ CD3+, CD4+, and CD8+ T cells was found in PB from patients with B cell non‐Hodgkin's lymphoma (B‐NHL) in comparison with healthy controls. Moreover, TOX+PD‐1+ and TOX+Tim‐3+ double‐positive T cells increased among the CD3+, CD4+, and CD8+T cell populations in the B‐NHL group. There was apparent heterogeneity in TOX expression and co‐expression with PD‐1, Tim‐3, and CD244 in CD3+, CD4+, and CD8+ T cells in different lymphoma patients. In addition, the percentage of CD4+CD25+FoxP3+ T cells (Treg) among the CD3+ and CD4+ T cells significantly increased, and the number of TOX+ and TOX+PD‐1+ Treg cells also significantly increased in the B‐NHL group. Conclusions: Higher expression of TOX concurrent with PD‐1, Tim‐3, and CD244 in T cells from patients with B‐NHL may contribute to T cell exhaustion and impair their special anti‐tumor T cell activity. TOX may be considered a potential target for reversing T cell exhaustion and improving T cell function in hematological malignancies. [ABSTRACT FROM AUTHOR]

To observe the effect of sufentanil combined with dezocine postoperative patient-controlled intravenous analgesia (PCIA) on pain stress and T cell subsets in patients undergoing laparoscopic radical gastrectomy. From January 2018 to July 2020, 97 patients undergoing laparoscopic radical gastrectomy in our hospital were selected, and they were divided into control group (48 cases, sufentanil postoperative PCIA) and observation group (49 cases, sufentanil combined with dezocine postoperative PCIA) by double color ball method. The pain and sedation [visual analogue scale (VAS) score, Ramsay score] at 2 h, 4 h, 8 h, 12 h and 24 h after operation were observed in the two groups. The changes of pain stress [β-endorphin, prostaglandin E2 (PEG2), substance P] and T cell subsets related indicators before and 24h after operation were observed in the two groups. The incidence of adverse reactions during analgesia was recorded in the two groups. VAS scores of observation group at 4 h, 8 h, 12 h and 24 h after operation were lower than that of control group (P<0.05). Ramsay scores of the observation group at 4 h, 8 h, 12 h and 24 h after operation were higher than that of the control group (P<0.05). 24 h after operation, the levels of serum β-endorphin, PEG2 and substance P of the observation group were lower than those of the control group (P<0.05). 24 h after operation, CD3+, CD4+, CD4+/CD8+ of the observation group were higher than those of the control group, and CD8+ was lower than that of the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). The application of sufentanil combined with dezocine in postoperative PCIA in patients undergoing laparoscopic radical gastrectomy has good sedative and analgesic effects, and good safety, which can further inhibit pain stress, and protect the immune function of patients. [ABSTRACT FROM AUTHOR]

Our objective was to investigate the inflammatory and oxidative stress markers in patients with moderate and severe form of coronavirus disease 2019 (COVID-19). In addition, we show the correlation between changes in lymphocyte subsets and markers of oxidative stress as a tool for patient classification. Interleukin-6 (IL-6) and VEGF were analyzed by utilizing a High Sensitivity Evidence Investigator™ Biochip Array technology. The total antioxidant capacity (PAT) and the free radical concentrations (d-ROM) were measured in serum utilizing analytical photometric system FRAS5. Peripheral blood was used to determine CD45 + mononuclear, B, T, and NK cells using a multi-parameter flow cytometric immunophenotypic test. Statistically significant differences in IL-6 and VEGF levels were observed between the two patient groups. Decreased values of the absolute number of lymphocytes and their CD4 + and CD8 + positive T cells, NK cells, and CD8 were obtained. In the moderate group, good correlations were found between IL-6 and VEGF and NK cells (r=0.6973, P<0.05; for IL-6 and r=0.6498, P<0, for VEGF. 05). Cytokines were correlated with CD45+ (r=0.5610, P<0.05; for IL-6 and r=0.5462, P<0.05 for VEGF). The oxidative stress index can be used as a cheaper alternative and as a triage tool between severe and moderate illnesses, after showing good correlation with more expensive patient classification analysis. [ABSTRACT FROM AUTHOR]

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objective: To investigate the effect of Fuzheng Jiedu formula combined with endu on lung function, T cell subsets and quality of life in patients with advanced non-small cell lung cancer (NSCLC). Methods: 116 patients with advanced NSCLC who were admitted to our hospital from March 2016 to October 2018 were randomly selected, patients were divided into two groups: control group (n=58, endu combined chemotherapy) and study group (n=58, combined with Fuzheng Jiedu formula on the basis of control group). The chemotherapy cycle was 21 days, with a total of 4 cycles. The curative effect and the incidence of adverse reactions were compared between the two groups. Lung function, T cell subsets and quality of life of the two groups before and 4 cycles after treatment were compared. Results: 4 cycles after treatment, the total clinical effective rate of the study group was 58.62% (34/58), which was higher than that of the control group 39.66% (23/58)(P<0.05). 4 cycles after treatment, the levels of CD4+, CD3+, CD4+/CD8+ in the two groups decreased, the study group was higher than that in the control group(P<0.05), the level of CD8+ increased, the study group was lower than the control group (P<0.05). The scores of physical function, cognitive function, role function, social function and emotional function, forced expiratory volume in the first second (FEV1), forced vital capacity(FVC), peak expiratory flow rate (PEF) were all increased in the two groups at 4 cycles after treatment, and those in the study group were higher than those in the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05). Conclusion: The Fuzheng Jiedu formula combined with endu has a good effect on patients with advanced NSCLC It can reduce the immunosuppression, improve the quality of life and lung function, and does not increase the incidence of adverse reactions. [ABSTRACT FROM AUTHOR]

Purpose: Immune checkpoint blockade (ICB) therapy shows little or no clinical benefit in most colorectal cancer (CRC) patients, due to the immunosuppressive T cell contexture in the tumor microenvironment (TME). Immunoglobulin-like transcript (ILT) 4 is an immunosuppressive molecule in myeloid cells. ILT4 is enriched in solid tumor cells, facilitating their proliferation, invasion, and metastasis. However, the regulatory role of ILT4 in T cell immunity of CRC is still undetermined. Here, we aimed to explore how tumor cell-derived ILT4 orchestrates T cell infiltration, subset distribution, and function in CRC. Methods: A total of 145 paraffin-embedded cancer tissues and the corresponding clinicopathological information were collected from CRC patients. Immunohistochemical (IHC) staining and public database analyses determined the correlation of ILT4 expression with different T cell subset densities, IFN-γ levels, and patient outcomes. Paired Ig-like receptor B (PIR-B, ILT4 mouse ortholog)-overexpressing/-downregulated MC38 cells were subcutaneously injected into C57BL/6 mice as a CRC transplantation model. The frequencies, subsets, and IFN-γ levels of T cells in mouse blood and spleens were determined using flow cytometry and immunohistochemistry, respectively. Results: High ILT4 expression in CRC cells was associated with decreased T cell infiltration, disease progression, and poor patient survival. T cell subset analyses indicated that ILT4-high patients showed reduced CD8+ T cell but elevated FOXP3+ regulatory T (Treg) cell frequencies in the TME. High ILT4 levels predicted lower IFN-γ production by tumor-infiltrating lymphocytes (TILs), especially by CD8+T cells in human CRC tissues. Moreover, PIR-B overexpression accelerated MC38 growth in mice, decreased CD3+/CD8+/IFN-γ+ T cell densities, and elevated Treg infiltration in the TME, blood, and spleens. PIR-B knockdown had the opposite effects. Conclusion: ILT4 in CRC cells induced immunosuppressive T cell subset infiltration and impaired IFN-γ production in TILs, suggesting that ILT4 might be a potential immunotherapeutic target and prognostic biomarker. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction–associated steatotic liver disease(MASLD), formerly known as non-alcoholic fatty liver disease(NAFLD), has become a major cause of chronic liver disease and a significant risk factor for hepatocellular carcinoma, which poses a huge burden on global public health and economy. MASLD includes steatotic liver disease, steatohepatitis, and cirrhosis, and the latter two cause great harm to human health and life, even complicated with liver cancer. Immunologic mechanism plays a major role in promoting its development into hepatitis and cirrhosis. Now more and more evidences show that T cells play an important role in the progression of MASLD. In this review, we discuss the double roles of T cells in MASLD from the perspective of T cell response pathways, as well as new evidences regarding the possible application of immunomodulatory therapy in MASH. • Introduce how antigen-presenting cells regulate T cell-mediated immune response and T cell differentiation, which helps to understand the immune balance in liver. • The roles of T cell subtypes and T cell cytokines in MASLD are introduced in depth. • T cells influence the development of MASLD, and here discuss the possibility of T cell immunotherapy in MASLD. [ABSTRACT FROM AUTHOR]

Objective: To observe the effects of immunoenhanced and common enteral nutrition preparations on nutritional status, intestinal mucosal barrier function and T-cell subsets in elderly with severe pneumonia. Methods: 136 elderly patients with severe pneumonia admitted to our hospital from July 2017 to March 2020 were selected, and randomly divided into study group(n=68), control group (n=68). The control group was treated with common enteral nutrition preparations for intervention, and the study group was treated with immuno enhanced enteral nutrition preparations for intervention. The incidence rarte of intestinal flora imbalance, nutritional status, intestinal mucosal barrier function, T cell subpopulation and complication rate were compared between the two groups. Results: The incidencer arte of intestinal flora imbalance in the study group was lower than that in the control group (P<0.05). No significant difference in incidence rate of complications between two groups (P>0.05). 10 d after intervention, the nutritional status indicators of the two groups: albumin (ALB), prealbumin (PAB) and hemoglobin (HGB) were higher than before intervention, and study group was higher than control group (P<0.05). 10d after intervention, functional indicators of intestinal mucosal barrier in the two groups: endotoxin (ET) and diamine oxidase (DAO) were lower than before intervention, and study group was lower than control group (P<0.05). 10 d after intervention, CD3+, CD4+, CD4+ /CD8+ in two groups were higher than before intervention, and study group was higher than control group (P<0.05), and CD8+ was lower than before intervention, and study group was lower than control group (P<0.05). Conclusion: Compared with common enteral nutrition preparations, immunoenhanced enteral nutrition preparations can improve the nutritional status of elderly patients with severe pneumonia, promote recovery of intestinal mucosal barrier function, improve the body's immune function, and reduce the incidence rate of intestinal flora imbalance [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the effect of moxifloxacin combined with fiber bronchoscopy drug perfusion on T cell subsets, lung function and liver function in patients with multi-drug resistant pulmonary tuberculosis. Methods: A total of 90 patients with multidrug-resistant tuberculosis admitted to our hospital from February 2017 to December 2018 were selected and divided into a control group (n=45, conventional basic treatment) and a study group (n=45) according to the random number table method., Moxifloxacin combined with fiber bronchoscopy drug perfusion), compare the negative rate of sputum bacteria, lesion absorption rate, T cell subsets, lung function and liver function between the two groups. Results: The negative conversion rate of sputum bacteria in the study group after 6 months of treatment was 88.89% (40/45), which was higher than 68.89% (31/45) in the control group (P<0.05). The lesion absorption rate in the study group after 6 months of treatment was 84.44% (38/45), which was higher than 64.44% (29/45) in the control group (P<0.05). After 6 months of treatment in the two groups, the first s forced expiratory volume (FEV1), forced vital capacity (FVC), maximum ventilation per minute (MVV) as a percentage of predicted value, total protein (TP), CD4+, CD4+/ CD8+ were all increased, and the study group was higher than the control group (P<0.05); alanine aminotransferase (ALT), aspartate aminotransferase (AST), CD8+ were all decreased, and the study group was lower Control group (P<0.05). Conclusion: Moxifloxacin combined with bronchofiberoscope drug perfusion for treatment of multi-drug resistant pulmonary tuberculosis can effectively prevent the disease from progressing. At the same time, it has a significant effect on improving patients' T cell subsets, lung function and liver function. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of Yupingfeng granules combined with recombinant human interferon α-1 b aerosol inhalation on inflammatory factors and T cell subsets in children with recurrent respiratory tract infection(RRTI). Methods: 180 children with RRTI who were admitted to our hospital from March 2018 to February 2020 were selected, children were divided into control group(n=90) and experimental group(n=90) according to the envelope lottery method. On the basis of routine treatment such as cough relief,antipyretic, antiasthmatic and anti infection, the children in the control group were treated with recombinant human interferonα-1 b aerosol inhalation. The children in the experimental group were treated with Yupingfeng granules on the basis of the control group. The curative effect, symptom disappearance time and inflammation factors, T cell subsets and adverse reactions of the two groups were compared. Results: The total clinical effective rate of the experimental group was 91.11%(82/90) at 3 weeks after treatment was higher than that 78.89%(71/90) of the control group(P<0.05). The disappearance time of lung rale, fever, wheeze, and cough of the experimental group were shorter than those of the control group(P<0.05). The levels of serum interleukin-6(IL-6), tumor necrosis factor-α(TNF-α) and interleukin-10(IL-10) in two groups at 3 weeks after treatment decreased, and the levels of the experimental group were lower than those of the control group(P<0.05). CD8~+decreased compared with that before treatment, and that in the experimental group was lower than that in the control group(P<0.05). CD4~+/CD8~+, CD3~+, CD4~+in two groups at 3 weeks after treatment increased,and the experimental group was higher than the control group(P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05). Conclusion: Yupingfeng granules combined with recombinant human interferon α-1 b aerosol inhalation in treatment of children with RRTI, which can rapidly improve the clinical symptoms, T cell subsets and inflammatory factors levels, and does not increase the incidence of adverse reactions, and the efficacy is satisfactory. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of different hemostasis methods on ovarian function, stress response and T cell subsets in patients with benign ovarian cysts during laparoscopic ovarian cyst removal. Methods: From January 2017 to January 2019, 80 patients with benign ovarian cysts in our hospital were selected, they were divided into group A (n=40) and group B (n=40). In group A, bipolar electrocoagulation was used for hemostasis, while in group B, suture was used for hemostasis. The ovarian function [follicle stim- ulating hormone (FSH), estradiol (E2) and luteinizing hormone (LH)], stress response [adrenocorticotropic hormone (ACTH), nore- pinephrine (NE) and cortisol (Cor)], T cell subsets and complications were compared between the two groups. Results: FSH and LH in- creased in both groups 3 months after operation, but group B was lower than group A (P<0.05). E2 decreased, but group B was higher than group A (P<0.05). ACTH, NE and Cor were all increased in the two groups 3 months after operation, but the levels in group B were lower than those in group A(P<0.05). CD3+, CD4+ /CD8+ and CD4+ decreased in the two groups 3 months after operation, but group B was higher than group A (P<0.05); CD8+ increased, but group B was lower than group A (P<0.05). There was no significant difference in the incidence of postoperative complications between the two groups (P>0.05). Conclusion: Compared with bipolar electrocoagulation hemostasis, suture hemostasis during laparoscopic ovarian cyst removal can reduce ovarian function damage, reduce stress response, and reduce immunosuppression, without increasing the incidence of complications. [ABSTRACT FROM AUTHOR]

To investigate the effect of Fuzheng Jiedu formula combined with gemcitabine and cisplatin on T cell sub- sets and serum tumor markers in patients with advanced non-small cell lung cancer (NSCLC). Methods: 80 patients with advanced NSCLC who were admitted to our hospital from March 2017 to December 2018 were selected, patients were divided into control group (n=40, treatmented with gemcitabine and cisplatin) and study group (n=40, treatmented with Fuzheng Jiedu Fang combined with gemcitabine and cisplatin) according to the random number method. The therapeutic effect, T cell subsets and serum tumor markers were com- pared between the two groups, and the adverse reactions of two groups were recorded. Results: The total clinical effective rate of the study group at 4 cycles after treatment was higher than that of the control group (P<0.05). CD3+, CD4+, CD4+ /CD8+ in the two groups at 4 cycles after treatment decreased compared with those before treatment, but the study group was higher than the control group (P<0.05). CD8+ in the two groups at 4 cycles after treatment increased compared with that before treatment, but the study group was lower than the control group (P<0.05). The levels of carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125) and carbohydrate antigen 199 (CA199) of the two groups at 4 cycles after treatment were lower than those before treatment, the study group was lower than the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion: Fuzheng Jiedu formula combined with gemcitabine and cisplatin in the treatment of advanced NSCLC patients, the effect is good, which can effectively prevent the progress of disease, reduce the immunosuppression, and has a good safety, and which has a certain clinical ap- plication value. [ABSTRACT FROM AUTHOR]

Through considerable effort in research and clinical studies, the immune system has been identified as a participant in the onset and progression of brain injury after ischaemic stroke. Due to the involvement of all types of immune cells, the roles of the immune system in stroke pathology and associated effects are complicated. Past research concentrated on the functions of monocytes and neutrophils in the pathogenesis of ischaemic stroke and tried to demonstrate the mechanisms of tissue injury and protection involving these immune cells. Within the past several years, an increasing number of studies have elucidated the vital functions of T cells in the innate and adaptive immune responses in both the acute and chronic phases of ischaemic stroke. Recently, the phenotypes of T cells with proinflammatory or anti-inflammatory function have been demonstrated in detail. T cells with distinctive phenotypes can also influence cerebral inflammation through various pathways, such as regulating the immune response, interacting with brain-resident immune cells and modulating neurogenesis and angiogenesis during different phases following stroke. In view of the limited treatment options available following stroke other than tissue plasminogen activator therapy, understanding the function of immune responses, especially T cell responses, in the post-stroke recovery period can provide a new therapeutic direction. Here, we discuss the different functions and temporal evolution of T cells with different phenotypes during the acute and chronic phases of ischaemic stroke. We suggest that modulating the balance between the proinflammatory and anti-inflammatory functions of T cells with distinct phenotypes may become a potential therapeutic approach that reduces the mortality and improves the functional outcomes and prognosis of patients suffering from ischaemic stroke. [ABSTRACT FROM AUTHOR]

Adoptive T cell therapy (ACT) holds great promise for cancer treatment. One approach, which has regained wide interest in recent years, employs antitumor T cells isolated from tumor lesions ("tumor-infiltrating lymphocytes" or TIL). It is now appreciated that a considerable proportion of anti-melanoma TIL recognize new HLA-binding peptides resulting from somatic mutations, which occurred during tumor progression. The clinical efficacy of TIL can potentially be improved via their genetic modification, designed to enhance their survival, homing capacity, resistance to suppression, tumor killing ability and additional properties of clinical relevance. Successful implementation of such gene-based strategies critically depends on efficient and reproducible protocols for gene delivery into clinical TIL preparations. Here we describe an optimized protocol for the retroviral transduction of TIL. As the experimental system we employed anti-melanoma TIL cultures prepared from four patients, recombinant retrovirus encoding an anti-CD19 chimeric antigen receptor (CAR) as a model gene of interest and CD19+ and CD19- human cell lines serving as target cells. Transduction on day 7 of the rapid expansion protocol (REP) resulted in 69 ± 8% CAR positive TIL. Transduced, but not untransduced TIL, from the four patients responded robustly to CD19+, but not CD19- cell lines, as judged by substantial secretion of IFN-γ following co-culture. In light of the rekindled interest in antitumor TIL, this protocol can be incorporated into a broad range of gene-based approaches for improving the in-vivo survival and functionality of TIL in the clinical setting. [ABSTRACT FROM AUTHOR]

Background: Ataxia-telangiectasia (AT) is a rare genetic condition, caused by biallelic deleterious variants in the ATM gene, and has variable immunological abnormalities. This study aimed to examine immunologic parameters reflecting cell development, activation, proliferation, and class switch recombination (CSR) and determine their relationship to the clinical phenotype in AT patients. Methods: In this study, 40 patients with a confirmed diagnosis of AT from the Iranian immunodeficiency registry center and 28 age-sex matched healthy controls were enrolled. We compared peripheral B and T cell subsets and T cell proliferation response to CD3/CD28 stimulation in AT patients with and without CSR defects using flow cytometry. Results: A significant decrease in naïve, transitional, switched memory, and IgM only memory B cells, along with a sharp increase in the marginal zone-like and CD21low B cells was observed in the patients. We also found CD4+ and CD8+ naïve, central memory, and terminally differentiated effector memory CD4+ (TEMRA) T cells were decreased. CD4+ and CD8+ effector memory, CD8+ TEMRA, and CD4+ regulatory T cells were significantly elevated in our patients. CD4+ T cell proliferation was markedly impaired compared to the healthy controls. Moreover, immunological investigations of 15 AT patients with CSR defect revealed a significant reduction in the marginal zone, switched memory, and more intense defects in IgM only memory B cells, CD4+ naïve and central memory T cells. Conclusion: The present study revealed that patients with AT have a broad spectrum of cellular and humoral deficiencies. Therefore, a detailed evaluation of T and B cell subsets increases understanding of the disease in patients and the risk of infection. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of adenoidectomy combined with tympanic intubation under nasal endoscopy on serum inflammatory factors and T cell subsets in children with secretory otitis media (SOM). Methods: From August 2016 to December 2018, 113 children with SOM in our hospital were selected. According to the random number table, the children were divided into the control group (n=56) and study group (n=57). The children in the control group were treated with tympanum catheterization, while the study group was treated with adenoidectomy under nasal endoscope on the basis of the control group. The efficacy, serum inflammatory factors and T cell subsets, time of middle ear effusion, average auditory valve in speech frequency area and complications of the two groups were compared. Results: The total clinical effective rate of the study group was 94.74%(54/57), which was higher than 75.00% (42/56) of the control group(P<0.05). The levels of serum interleukin-2(IL-2), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) of the two groups decreased at 3 months after operation, and the levels of the study group were lower than those of the control group (P<0.05). 3 months after operation, CD8+ decreased of the two groups, and it in the study group was lower than that in the control group (P<0.05). CD4+, CD4+/CD8+ increased, and those in the study group were higher than those in the control group(P<0.05). The time of middle ear effusion in the study group was shorter than that in the control group, and the average auditory valve in the speech frequency area was higher than that in the control group(P<0.05). There was no significant difference between the two groups in postoperative complications (P>0.05). Conclusion: Adenoidectomy combined with tympanic intubation under nasal endoscopy is effective in the treatment of SOM children. It can effectively improve the serum inflammatory factors, T cell subsets, the time of middle ear effusion and the average auditory valve in the speech frequency area. It has good safety and high clinical application value. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of rifabutin combined with moxifloxacin in the treatment of multidrug resistant tuberculosis and its effect on inflammatory factors and T cell subsets. Methods: From June 2016 to June 2018, 110 multidrug resistant tuberculosis patients in our hospital were selected. The patients were divided into control group (n = 55) and study group (n = 55) according to the random number table method. The patients in the control group were treated with rifabutin capsule combined with levofloxacin, while those in the study group were treated with rifabutin capsule combined with moxifloxacin. The curative effect, inflammatory factors and T cell subsets levels of the two groups were compared. The adverse reactions of the two groups were recorded during the treatment. Results: The absorption rate of focus, the rate of cavity closure and the negative rate of sputum bacteria in the study group at 12 months after treatment and 18 months after treatment were higher than those in the control group (P<0.05). 18 months after treatment, tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP) were lower than those before treatment, and the study group was lower than control group (P<0.05). 18 months after treatment, CD4+/CD8+ and CD4+ in two groups were higher than those before treatment, and the study group was higher than those control group (P<0.05). CD8+ was lower than before treatment, and that in the study group was lower than that in the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion: Rifabutin capsule combined with moxifloxacin is effective in the treatment of multidrug resistant tuberculosis. It can effectively improve the inflammatory factors and T cell subsets, and has good safety, and high clinical application value. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of transcutaneous acupoint electrical stimulation (TEAS) combined with general anesthesia on inflammatory factors, T cell subsets and cognitive function in patients undergoing laparoscopic radical resection of colorectal cancer. Methods: 90 patients who underwent laparoscopic colorectal cancer radical surgery in our hospital were selected from June 2018 to September 2019, they were divided into control group (n=45) and study group (n=45) according to the random number table method. The control group was given general anesthesia. The study group combined with TEAS on the basis of the control group. Inflammatory factors, T cell subsets, cognitive function and pain were compared between the two groups. Results: The levels of interleukin-6 (IL-6), interleukin-1 (IL-1), tumor necrosis factor-琢(TNF-琢) in the study group at 1 d after operation, 5 d after operation were lower than those in the control group (P<0.05). CD3+, CD4+/CD8+ and CD4+ in the study group were higher than those in the control group at 1d after operation, 5d after operation, while CD8+ was lower than that in the control group (P<0.05). The scores of simple mental state Checklist (MMSE) in the study group were higher than those in the control group at 1d after operation, 3 d after operation, 4 d after operation, 7d after operation (P<0.05). The visual analogue scale (VAS) score of the study group was lower than that of the control group at 6 h after operation, 12 h after operation, 24 h after operation, 48 h after operation (P<0.05). There was no significant difference in the incidence of cognitive impairment (POCD) between the two groups on the 5th and 7th postoperative days (P>0.05); the incidence of POCD in the study group at 5d after operation, 7d after operation was lower than that in the control group (P<0.05). Conclusion: TEAS combined with general anesthesia can reduce inflammatory response, immune suppression and cognitive impairment in patients undergoing laparoscopic colorectal cancer radical resection. [ABSTRACT FROM AUTHOR]

T cells responding to acute infections generally provide two key functions to protect the host: (1) active contribution to pathogen elimination and (2) providing long‐lived cells that are poised to rapidly respond to renewed infection, thus ensuring long‐lasting protection against the particular pathogen. Extensive work has established an astonishing amount of additional diversity among T cells actively contributing to pathogen elimination, as well as among resting, long‐lived antigen‐experienced T cells. This led to the description of a variety of functionally distinct T cell 'subsets'. Understanding how this heterogeneity develops among T cells responding to the same antigen is currently an active area of research, since knowledge of such mechanisms may have implications for the development of vaccines and immunotherapy. The number of naïve T cells specific to a given antigen span a great range. Considering this, one mechanistic angle focusses on how individual naïve T cells contribute to the development of the distinct T cell subsets. In this review, we highlight the current technologies that enable one to address the contributions of individual naïve T cells to different T cell subsets, with a focus on CD8 T cell subsets generated in the context of acute infections. Moreover, we discuss the requirements of new technologies to further our understanding of the mechanisms that help generate long‐lasting immunity. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of budesonide combined with terbutaline inhalation on tidal breathing pulmonary function, T cell subsets and serum inflammatory factors in children with bronchiolitis. Method: 98 children with bronchiolitis in our hospital from January 2019 to December 2019 were selected, and they were randomly divided into control group (conventional treatment) and observation group (budesonide combined with terbutaline inhalation on the basis of the control group), 49 cases in each group. The total effective rate of the two groups 1 week after treatment was recorded. The indexes of tidal breathing pulmonary function [inspiratory/expiratory time ratio (Ti/TE), time to peak ratio (tptef/TE), peak volume ratio (VPEF/VE), tidal volume per kilogram (VT/kg)], T cell subsets [CD3+, CD4+, CD8+ and CD4+ /CD8+ ], serum inflammatory factors [procalcitonin (PCT), C-reactive protein (CRP)] were compared between the two groups before and 1 week after treatment. The incidence of adverse reactions was compared between the two groups. Result: The total effective rate of the observation group was 91.84% (45/49), which was higher than 69.39% (34/49) of the control group 1 week after treatment, and the difference was statistically significant (P<0.05). 1 week after treatment, Ti/Te, TPTEF/TE, VPEF/VE, Vt/kg, CD3+, CD4+, CD4+ /CD8+ of the two groups were higher than those before treatment, and the observation group was higher than the control group (P<0.05), PCT, CRP, CD8+ were lower than before treatment, and the observation group was lower than the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion: [ABSTRACT FROM AUTHOR]

To investigate the effect of laparoscopic and open wedge resection on the nutritional status, T cell subsets and prognosis of patients with gastric stromal tumor (GIST). The clinical data of 97 patients with GIST in our hospital from January 2013 to February 2014 were retrospectively selected. According to the different operation methods, the patients were divided into the control group (n=47, open stomach wedge resection) and study group (n=50, laparoscopic stomach wedge resection). The operation related indexes, nutritional status, T cell subsets and prognosis of the two groups were compared. The time of hospitalization, anal exhaust, incision length and operation in the study group were shorter than those in the control group, and the amount of bleeding in the operation was less than that in the control group (P<0.05). The prealbumin, transferrin and albumin in the two groups at 7 days after operation were lower than those before operation, but those in the study group were higher than those in the control group (P<0.05). The CD4+ /CD8+, CD3+, CD4+ in the two groups at 7 days after operation were lower than those before operation, while CD8+ was higher than that before operation (P<0.05). The CD4+ /CD8+, CD3+, CD4+ in the study group at 7 days after operation were higher than those in the control group, while CD8+ was lower than that in the control group (P<0.05). The total incidence rate of complications in the study group was lower than that in the control group (P<0.05). There were no differences in the postoperative recurrence rate and 5-year survival rate between the two groups (P>0.05). Compared with open stomach wedge resection, the long-term prognosis of GIST patients treated with laparoscopic gastric wedge resection is similar, it can effectively improve the perioperative related indicators, it has less impact on the nutritional status and T cell subsets of patients, and reduce the incidence of postoperative complications. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of laparoscopic and open wedge resection on the nutritional status, T cell subsets and prognosis of patients with gastric stromal tumor (GIST). Methods: The clinical data of 97 patients with GIST in our hospital from January 2013 to February 2014 were retrospectively selected. According to the different operation methods, the patients were divided into the control group (n=47, open stomach wedge resection) and study group (n=50, laparoscopic stomach wedge resection). The operation related indexes, nutritional status, T cell subsets and prognosis of the two groups were compared. Results: The time of hospitalization, anal exhaust, incision length and operation in the study group were shorter than those in the control group, and the amount of bleeding in the operation was less than that in the control group (P<0.05). The prealbumin, transferrin and albumin in the two groups at 7 days after operation were lower than those before operation, but those in the study group were higher than those in the control group (P<0.05). The CD4+/CD8+, CD3+, CD4+ in the two groups at 7 days after operation were lower than those before operation, while CD8+ was higher than that before operation (P<0.05). The CD4+/CD8+, CD3+, CD4+ in the study group at 7 days after operation were higher than those in the control group, while CD8+ was lower than that in the control group (P<0.05). The total incidence rate of complications in the study group was lower than that in the control group (P<0.05). There were no differences in the postoperative recurrence rate and 5-year survival rate between the two groups (P>0.05). Conclusion: Compared with open stomach wedge resection, the long-term prognosis of GIST patients treated with laparoscopic gastric wedge resection is similar, it can effectively improve the perioperative related indicators, it has less impact on the nutritional status and T cell subsets of patients, and reduce the incidence of postoperative complications. [ABSTRACT FROM AUTHOR]