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Mycobacterium bovis , the causative agent of bovine tuberculosis (bTB), is a zoonotic pathogen that contributes to economic losses in the cattle industry and poses a public health risk worldwide. Bacillus Calmette-Guerin, or BCG, is a live attenuated strain of M. bovis that is used for human vaccination against tuberculosis and is considered a potential vaccine candidate against bTB. However, BCG affords widely variable levels of protection against challenge and interferes with current diagnostic methods, and as such, it is not currently approved for use as a livestock or wildlife vaccine in the United States. Many efforts have been made to develop bTB vaccines that are reliable and do not interfere with diagnostic testing, but BCG continues to be the most effective option. Previous work has shown that a T helper 1 immune response is essential for protection against virulent M. bovis infection, characterized by CD4+ central and effector memory T cells. In an effort to identify an efficacious bTB intervention strategy, the study presented here used an in vitro recall response assay and concurrent evaluation of CD4+ T cell proliferation and cytokine production to characterize the surface and functional phenotypes of memory responses to BCG vaccination in cattle. Our findings enhance understanding of the bovine immune response to BCG and provide insights into the development of improved vaccines for the control of bTB. [ABSTRACT FROM AUTHOR]

Mycobacterium bovis, the causative agent of bovine tuberculosis (bTB), is a zoonotic pathogen that contributes to economic losses in the cattle industry and poses a public health risk worldwide. Bacillus Calmette-Guerin, or BCG, is a live attenuated strain of M. bovis that is used for human vaccination against tuberculosis and is considered a potential vaccine candidate against bTB. However, BCG affords widely variable levels of protection against challenge and interferes with current diagnostic methods, and as such, it is not currently approved for use as a livestock or wildlife vaccine in the United States. Many efforts have been made to develop bTB vaccines that are reliable and do not interfere with diagnostic testing, but BCG continues to be the most effective option. Previous work has shown that a T helper 1 immune response is essential for protection against virulent M. bovis infection, characterized by CD4+ central and effector memory T cells. In an effort to identify an efficacious bTB intervention strategy, the study presented here used an in vitro recall response assay and concurrent evaluation of CD4+ T cell proliferation and cytokine production to characterize the surface and functional phenotypes of memory responses to BCG vaccination in cattle. Our findings enhance understanding of the bovine immune response to BCG and provide insights into the development of improved vaccines for the control of bTB.

Gang Chen,1 Qing Mu,1 Zhao-Ji Meng2 1Department of Respiratory and Critical Care Medicine, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Immune Allergy, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Gang Chen, Department of Respiratory and Critical Care Medicine, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, 7 Weiwu Road, Zhengzhou, Henan, 450003, People’s Republic of China, Email chengangvips@163.comBackground: Dysregulation and pyroptosis of T-helper (Th) cells and inflammatory cytokines have been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the immune response mechanisms as a consequence of tobacco smoke exposure are not fully understood. We hypothesized that cigarette smoke-induced inflammation could be modulated through the cytokine milieu and T-cell nicotinic acetylcholine receptors (nAChRs).Methods: The proportions of peripheral blood Th1 and Th2 cells from patients with COPD, smokers without airway obstruction and healthy nonsmokers were analyzed using flow cytometry. The levels of plasma proinflammatory cytokines and their potential association with pulmonary function were also measured. The influence of cigarette smoke extract (CSE) on the conditioned differentiation of T helper cell subsets was further examined in vitro.Results: Significantly higher Th1 cell and plasma IFN-γ and IL-18 levels but lower levels of Th2 cells were found in the peripheral blood from patients with COPD. The increased plasma levels of IFN-γ and IL-18 were negatively correlated with pulmonary function (FEV1% predicted value). Pyroptosis participates in COPD development probably through the activation of the NLRP3 inflammasome upon exposure to CSE. CSE does not directly induce the differentiation of T helper cells; however, under conditioned medium, CSE promotes Th1 development through α 7 nAChR modification, while it does not substantially interfere with Th2 differentiation.Conclusion: The differences in the cytokine milieu play a key role in the effects of CSE on the immune response in patients with COPD.Keywords: chronic obstructive pulmonary disease, COPD, cigarette smoke, T helper 1, Th1 cells, Th2, nicotinic acetylcholine receptors, nAChRs

Hanan E Alrashidi,1 Amna A Alotiby2 1Medical Laboratory Technology Department, Faculty of Applied Medical Sciences, Taibah University, Madinah, Saudi Arabia; 2Haematology and Immunology Department, College of Medicine, Umm Al-Qura University, Makkah, Saudi ArabiaCorrespondence: Amna A Alotiby, Haematology and Immunology Department, College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia, Email aamogaty@uqu.edu.saIntroduction: Zinc is essential for the growth and differentiation of immune cells. Zinc insufficiency affects immune system function, thereby increasing infection susceptibility, autoimmunity, and allergies. Here, we aimed to determine the effects of zinc supplementation on T cell subpopulations, regulatory T (Tregs), T helper 1 (Th1), and T helper 17 (Th17) cells, in mixed lymphocyte cultures (MLC).Methods: Allogeneic immune reactions were imitative using mixed lymphocyte cultures, followed by incubation with zinc to further monitor their effects. Cells were analyzed by flow cytometry. Production of Interferon-gamma (IFNγ), Interleukin-17 A (IL17A), and IL10 were analyzed by enzyme-linked immunosorbent assay. Th1 cell-specific Tbet, Th17 cell-specific RORC2, and Tregs-specific Foxp3 expression levels were determined by quantitative real-time PCR.Results: Zinc supplementation at a physiological dose significantly increased CD4+ Foxp3+ Tregs and CD25+ Foxp3+ Tregs numbers and slightly decreased CD4+ RORC2+ and CD25+ RORC2+ Th17 cell numbers. A significant reduction in IFNγ production was observed in both restimulated T cells with autologous peripheral blood mononuclear cell (PBMC) and allogeneic PBMC compared to that in untreated T cells. Zinc significantly reduced IL17 expression, but the increase in IL10 expression was insignificant. In zinc-supplemented MLC, a non-significant decrease in Th1 or Th17 cell-specific transcription factors expression was observed, whereas there was a significant increase in Tregs-specific transcription factor expression.Conclusion: Zinc can stabilize Tregs participating in adverse immune reactions or in an in vitro transplantation model.Keywords: zinc, T helper 1, T helper 17, T regulatory, mixed lymphocyte culture

Introduction: Premenstrual syndrome (PMS) and primary dysmenorrhea (PD) are common gynecological complications and there is evidence that inflammation may be an important factor in their etiology. There is a relationship between PMS and PD with susceptibility to allergic disorders. We aimed to assess the effect of curcumin co-administered with piperine on serum IL-10, IL-12 and IgE levels in patients with PD and PMS.Materials and Methods: A sample of 80 patients were recruited to this triple-blind, placebo-controlled clinical trial. Participants were randomly allocated to curcumin (n = 40) and control groups (n = 40). Each participant received one capsule (500 mg of curcuminoid plus piperine, or placebo) daily, from 7 days before until 3 days after menstruation for three consecutive menstrual cycles.Results: Serum IgE, IL-10 and IL-12 levels were quantified by using an ELISA kit. No significant differences were found between the two groups at baseline, including: age, BMI, and dietary intakes (P > 0.05). Curcumin + piperine treatment was associated with a significant reduction in the mean serum levels of IgE [from 223.6 ± 258.7 IU/mL to 161.3 ± 240.7; P = 0.001]; but there were no significant changes in the placebo group (P = 0.12). Serum concentrations of IL-10 and IL-12 before and after the trial period did not differ significantly between the two groups (P > 0.05).Conclusion: Curcumin plus piperine might be have positive effect on serum IgE levels with no significant changes on serum IL-10 and IL-12 in healthy young women with PMS and PD. Studies with higher doses and longer durations of treatment with curcumin are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Although polymyalgia rheumatica (PMR) is a very common rheumatic inflammatory disease, current insight into the pathobiology of PMR is limited and largely based on studies in blood. We investigated T helper 1 (TH1) and T helper 17 (TH17) cell responses in blood, synovial fluid and bursa tissue of patients with PMR. Materials and methods: Blood samples were collected from 18 patients with new-onset PMR and 32 healthy controls. Synovial fluid was aspirated from the inflamed shoulder bursae or biceps tendon sheath of 13 patients. Ultrasound-guided biopsies of the subacromial-subdeltoid (SASD) bursa were obtained from 11 patients. T cells were examined by flow cytometry, immunohistochemistry and immunofluorescence staining. Results: Besides an increase of TH17 (CD4+IL-17+IFN-γ-) cells and T cytotoxic 17 (TC17; CD8+IL-17+IFN-γ-) cells, no other major changes were noted in the circulating T cell compartment of patients with PMR. Absolute numbers of CD4+ and CD8+ T cells were similar in blood and synovial fluid of patients with PMR. Synovial fluid T cells showed an effector-memory (CD45RO+CCR7-) phenotype. Percentages of TH1 (CD4+IFN-γ+IL-17-) cells and TH1/TH17 (CD4+IFN-γ+IL-17+) cells, but not TH17 or TC17 cells, were increased in the synovial fluid. Bursa tissue biopsies contained a small number of T cells, which were mostly CD8 negative. The majority of bursa tissue T cells produced IFN-γ but not IL-17. For comparison, B cells were scarcely detected in the bursa tissue. Conclusion: Although the circulating TH17 cell pool is expanded in patients with PMR, our findings indicate that TH1 cells are involved in the inflammation of bursae and tendon sheaths in this condition. Our study points towards the TH1 cell pathway as a potential target for therapy in PMR. [ABSTRACT FROM AUTHOR]

Most pathogens infect through mucosal surfaces, and parenteral immunization typically fails to induce effective immune responses at these sites. Development of oral-administered vaccines capable of inducing mucosal as well as systemic immunity while bypassing the issues of antigen degradation and immune tolerance could be crucial for the control of enteropathogens. This study demonstrates that U-Omp19, a bacterial protease inhibitor with immunostimulatory features, coadministered with Salmonella antigens by the oral route, enhances mucosal and systemic immune responses in mice. U-Omp19 was able to increase antigen-specific production of IFN-γ and IL-17 and mucosal (IgA) antibody response. Finally, oral vaccination with U-Omp19 plus Salmonella antigens conferred protection against virulent challenge with Salmonella Typhimurium, with a significant reduction in bacterial loads. These findings prove the efficacy of this novel adjuvant in the Salmonella infection model and support the potential of U-Omp19 as a suitable adjuvant in oral vaccine formulations against mucosal pathogens requiring T helper (Th)1-Th17 protective immune responses.

BackgroundAlthough polymyalgia rheumatica (PMR) is a very common rheumatic inflammatory disease, current insight into the pathobiology of PMR is limited and largely based on studies in blood. We investigated T helper 1 (TH1) and T helper 17 (TH17) cell responses in blood, synovial fluid and bursa tissue of patients with PMR.Materials and methodsBlood samples were collected from 18 patients with new-onset PMR and 32 healthy controls. Synovial fluid was aspirated from the inflamed shoulder bursae or biceps tendon sheath of 13 patients. Ultrasound-guided biopsies of the subacromial-subdeltoid (SASD) bursa were obtained from 11 patients. T cells were examined by flow cytometry, immunohistochemistry and immunofluorescence staining.ResultsBesides an increase of TH17 (CD4+IL-17+IFN-γ-) cells and T cytotoxic 17 (TC17; CD8+IL-17+IFN-γ-) cells, no other major changes were noted in the circulating T cell compartment of patients with PMR. Absolute numbers of CD4+ and CD8+ T cells were similar in blood and synovial fluid of patients with PMR. Synovial fluid T cells showed an effector-memory (CD45RO+CCR7-) phenotype. Percentages of TH1 (CD4+IFN-γ+IL-17-) cells and TH1/TH17 (CD4+IFN-γ+IL-17+) cells, but not TH17 or TC17 cells, were increased in the synovial fluid. Bursa tissue biopsies contained a small number of T cells, which were mostly CD8 negative. The majority of bursa tissue T cells produced IFN-γ but not IL-17. For comparison, B cells were scarcely detected in the bursa tissue.ConclusionAlthough the circulating TH17 cell pool is expanded in patients with PMR, our findings indicate that TH1 cells are involved in the inflammation of bursae and tendon sheaths in this condition. Our study points towards the TH1 cell pathway as a potential target for therapy in PMR.

The skin functions as a protective barrier to inhibit the entry of foreign pathogens, all the while hosting a diverse milieu of microorganisms. Over time, skin cells, immune cells, cytokines, and microbes interact to integrate the processes of maintaining the skin’s physical and immune barrier. In the present study, the basal expression of two immunologically divergent mouse strains C57BL/6 and BALB/c, as well as a strain on the C57 background lacking IL-6, was characterized. Additionally, cutaneous antimicrobial gene expression profiles and skin bacterial microbiome were assessed between strains. Total RNA sequencing was performed on untreated C57BL/6 (control), BALB/c, and IL-6-deficient skin samples and found over 3,400 genes differentially modulated between strains. It was found that each strain modulated its own transcriptional “profile” associated with skin homeostasis and also influenced the overall bacterial colonization as indicated by the differential phyla present on each strain. Together, these data not only provide a comprehensive view of the transcriptional changes in homeostatic skin of different mouse strains but also highlight the possible influence of the strain differences (e.g., Th1/Th2 balance) as well as a role for IL-6 in overall skin immunity and resident microbial populations.

The skin functions as a protective barrier to inhibit the entry of foreign pathogens, all the while hosting a diverse milieu of microorganisms. Over time, skin cells, immune cells, cytokines, and microbes interact to integrate the processes of maintaining the skin's physical and immune barrier. In the present study, the basal expression of two immunologically divergent mouse strains C57BL/6 and BALB/c, as well as a strain on the C57 background lacking IL-6, was characterized. Additionally, cutaneous antimicrobial gene expression profiles and skin bacterial microbiome were assessed between strains. Total RNA sequencing was performed on untreated C57BL/6 (control), BALB/c, and IL-6-deficient skin samples and found over 3,400 genes differentially modulated between strains. It was found that each strain modulated its own transcriptional "profile" associated with skin homeostasis and also influenced the overall bacterial colonization as indicated by the differential phyla present on each strain. Together, these data not only provide a comprehensive view of the transcriptional changes in homeostatic skin of different mouse strains but also highlight the possible influence of the strain differences (e.g., Th1/Th2 balance) as well as a role for IL-6 in overall skin immunity and resident microbial populations. [ABSTRACT FROM AUTHOR]

There is very little knowledge about the immune responses, particularly cellular immunity to coronavirus disease 2019 (COVID‐19). The main objective of this study was to evaluate the frequency of T helper (Th) cell subtypes, including Th1, Th17, and Treg cells, in moderate‐to‐severe and critical COVID‐19 patients compared to healthy controls. Twenty‐nine moderate‐to‐severe and 13 critical patients confirmed for COVID‐19, and 15 healthy subjects were included in this study. Interferon‐γ (IFN‐γ)‐producing Th1 and interleukin‐17A‐producing Th17 and Treg cells in peripheral blood were measured with flow cytometry. The frequency of Th1 and Th17 was significantly decreased in critical patients compared to healthy subjects (aMD: −2.76 and − 2.34) and moderate‐to‐severe patients (aMD: −1.89 and − 1.89), respectively (p < 0.05). Differences were not significant between moderate‐to‐severe patients and healthy subjects for both Th1 (p = 0.358) and Th17 (p = 0.535), respectively. In contrast, significant difference was not observed between study subjects regarding the frequency of Treg cells. Patients with critical COVID‐19 had a markedly lower Th1/Treg and Th17/Treg ratios compared with the controls and moderate‐to‐severe cases. Our study showed a dysregulated balance of Th1 and Th17 cells and its relation to the severity of COVID‐19. [ABSTRACT FROM AUTHOR]

Influenza A virus (IAV) is the major cause of seasonal epidemics and flu outbreaks worldwide. Given that interleukin 16 (IL16) can regulate T cell function and is one of the signature markers for virus infection including IAV infection, the impact of IL16 on IAVinduced T cell immune response hasn't been elucidated yet. In this paper, we infected wild type and IL16 knockout (KO) mice with IAV and analyzed the immunity of mice by flow cytometry. We observed an increase in the percentage of T helper (Th) 1 cells in the spleens of IL16 KO mice and elevation of IFN-α and TNF-α secretion from CD8+ T cells in the lungs and spleens of IL16 KO mice in response to IAV infection. Moreover, the expression of major histocompatibility complex II which represents the maturation of dendritic cells (DCs) was upregulated in the lungs of IL16 KO mice. Taken together, our study suggests that IL16 deficiency enhanced Th1 and cytotoxic T lymphocyte response as well as DC maturation upon IAV infection, which provides new insight into the host regulation of T cell immune responses during IAV infection. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a type of inflammatory and demyelinating disorder of the central nervous system in which immune‐mediated inflammatory processes are elicited by secreted cytokines from T helper (Th)‐1 and Th17 cells. While some protein‐coding genes expressed in T cell types have established involvement in MS disease progression, little is understood about the roles of long noncoding RNAs (lncRNAs) within the disease landscape. LncRNAs, noncoding RNAs longer than 200 nucleotides, likely control gene expression and function of Th1 cells, and offer the potential to act as therapeutic and biomarker candidates for MS. We identified lncRNAs in Th1 cells linked to MS. Expression levels of candidate lncRNAs and genes were evaluated in 50 MS patients and 25 healthy controls using quantitative real‐time polymerase chain reaction, and their correlations were assessed. LncRNAs encoded by AC007278.2 and IFNG‐AS1‐001 showed significantly higher expression in relapsing Phase MS patients whereas IFNG‐AS1‐003 was elevated in patients in the remitting phase compared with relapsing patients. Collectively, these misregulated lncRNAs may provide valuable tools to understand the relationships between lncRNAs and MS, and possibly other related disorders. [ABSTRACT FROM AUTHOR]

Mature T helper (Th) effector cells originate following antigen recognition by naive T precursors. The maturation process is accompanied by the acquisition of specific effector functions that distinguish at least three different T helper subsets: Th1, Th2 and Th17. In general, maturation of somatic cells is accompanied by terminal differentiation. However, accumulating evidence shows that effector T cells retain a certain degree of plasticity. This is especially true for Th17 cells, which have been shown to converge towards other phenotypes in response to specific microenvironmental pressure. In this review we will discuss the experimental evidence that supports the hypothesis of Th17 plasticity, with particular emphasis on the generation of Th17‐derived 'non‐classic' Th1 cells, and the molecular networks that control it. Moreover, we will consider why Th17 plasticity is important for host protection, but also why it can have pathogenic functions during chronic inflammation. Regarding the last point, we will discuss a possible role for biological drugs in the control of Th17 plasticity and disease course. [ABSTRACT FROM AUTHOR]

Individual CD4+ T cells can become one of a number of helper (Th) lineages with distinct effector functions. However, whether biases in Th potential exist prior to antigen encounter is unknown. Studies have identified cell‐intrinsic functional heterogeneity among naïve T cells that can be parsed based on the strength of T‐cell receptor (TCR) interactions with self‐peptide. Here, using CD5 levels as a surrogate for the strength of these basal TCR signals, we sought to identify pre‐existing effector biases in the CD4+ T‐cell lineage. We show that ex vivo‐activated CD5loCD4+ T cells produce greater amounts of the Th1 cytokine interferon‐gamma (IFNγ) than their CD5hi counterparts. In addition, a greater percentage of CD5lo effector CD4+ T cells produce IFNγ in both polyclonal and monoclonal CD4+ T‐cell populations after antigen challenge in vivo. These results suggest that differential IFNγ production potential exists among CD4+ T cells prior to activation and independent of TCR affinity for foreign antigen. [ABSTRACT FROM AUTHOR]

Abstract Enteric redmouth disease (ERM or yersiniosis) is one of the most important diseases of salmonids and leads to significant economic losses. It is caused by the Gram-negative bacterium Yersinia ruckeri but can be controlled by bacterin vaccination. The first commercial ERM vaccine was licenced in 1976 and is one of the most significant and successful health practices within the aquaculture industry. Although ERM vaccination provides complete protection, knowledge of the host immune response to the vaccine and the molecular mechanisms that underpin the protection elicited is limited. In this report, we analysed the expression in spleen and gills of a large set of genes encoding for cytokines, acute phase proteins (APPs) and antimicrobial peptides (AMPs) in response to ERM vaccination in rainbow trout, Oncorhynchus mykiss. Many immune genes in teleost fish are known to have multiple paralogues that can show differential responses to ERM vaccination, highlighting the necessity to determine whether all of the genes present react in a similar manner. ERM vaccination immediately activated a balanced inflammatory response with correlated expression of both pro- and anti-inflammatory cytokines (eg IL-1β1-2, TNF-α1-3, IL-6, IL-8 and IL-10A etc.) in the spleen. The increase of pro-inflammatory cytokines may explain the systemic upregulation of APPs (eg serum amyloid A protein and serum amyloid protein P) and AMPs (eg cathelicidins and hepcidin) seen in both spleen and gills. We also observed an upregulation of all the α-chains but only one β-chain (p40B2) of the IL-12 family cytokines, that suggests specific IL-12 and IL-23 isoforms with distinct functions might be produced in the spleen of vaccinated fish. Notably the expression of Th1 cytokines (IFN-γ1-2) and a Th17 cytokine (IL-17A/F1a) was also up-regulated and correlated with enhanced expression of the IL-12 family α-chains, and the majority of pro- and anti-inflammatory cytokines, APPs and AMPs. These expression profiles may suggest that ERM vaccination activates host innate immunity and expression of specific IL-12 and IL-23 isoforms leading to a Th1 and Th17 biased immune response. A late induction of Th2 cytokines (IL-4/13B1-2) was also observed, that may have a homeostatic role and/or involvement in antibody production. This study has increased our understanding of the host immune response to ERM vaccination and the adaptive pathways involved. The early responses of a set of genes established in this study may provide essential information and function as biomarkers in future vaccine development in aquaculture. Highlights • ERM vaccination activates both pro- and anti-inflammatory cytokine expression in spleen. • ERM vaccination upregulates APP and AMP expression in both spleen and gills. • ERM vaccination induces the expression of specific IL-12 and IL-23 isoforms in spleen. • ERM vaccination initiates a Th1/Th17 biased immune response in spleen. [ABSTRACT FROM AUTHOR]

Adipose-derived mesenchymal stem cells (Ad-MSCs) have been reported to suppress the effector T cell responses and have beneficial effects on various immune disorders, like rheumatoid arthritis (RA). This study was designed to investigate the effects of co-cultured Ad-MSCs on peripheral blood mononuclear cells (PBMCs) of RA patients and healthy individuals, through assessing transcription factors of T cell subsets. PBMCs from RA patients and healthy donors were co-cultured with Ad-MSCs with or without Phytohaemagglutinin (PHA). The quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression of T-box 21 (T-bet), GATA-binding protein-3 (GATA3), retinoid-related orphan receptor γt (ROR-γt) and forkhead box P3 (Foxp3). Based on the results, Ad-MSCs greatly upregulated Th2 and Treg cell transcription factors, i.e., GATA3 and Foxp3 (p<0.05), and downregulated Th1 and Th17 transcription factors, i.e., T-bet and RORγt (p<0.05). These results demonstrate that Ad-MSCs can result in an immunosuppressive environment through inhibition of pro-inflammatory T cells and induction of T cells with a regulatory phenotype. Therefore, they might have important clinical implications for inflammatory and autoimmune diseases such as RA. [ABSTRACT FROM AUTHOR]

Mammalian interleukin (IL)-2 is a cytokine centrally involved in the differentiation and survival of CD4+ T helper subsets and CD4+ T regulatory cells and in activation of cytotoxic effector lymphocytes. In bony fish, IL2 orthologs have been identified with an additional divergent IL2-Like gene on the same locus present in several fish species. We report here two divergent IL2 paralogs, IL2A and IL2B, in salmonids that originated from the whole genome duplication event in this fish lineage. The salmonid IL2 paralogs differ not only in sequence but also in exon sizes. The IL-2 isoforms that are encoded have disparate pI values and may have evolved to preferentially bind specific IL-2 receptors. Rainbow trout IL2 paralogs are highly expressed in thymus, spleen, gills, kidney and intestine, important tissues/organs in fish T cell development and function. Their expression in peripheral blood leukocytes (PBL) is low constitutively but can be upregulated by the mixed leukocyte reaction, by the T cell mitogen phytohemagglutinin and by signal mimics of T cell activation (phorbol 12-myristate 13-acetate and calcium ionophore). Both trout IL-2 isoforms promoted PBL proliferation and sustained high-level expression of CD4 and CD8, suggesting that trout IL-2 isoforms are T cell growth/survival factors mainly expressed by activated T cells. The recombinant proteins for these two trout IL2 paralogs have been produced in E. coli and possess shared but also distinct bioactivities. IL-2A, but not IL-2B, induced IL12P35A1 and CXCR1 expression in PBL. IL-2B had a stronger effect on upregulation of the T helper 1 (Th1) cytokine interferon-γ (IFNγ) and could sustain CD8α and CD8β expression levels. Nevertheless, both cytokines upregulated key Th1 (IFNγ1, IFNγ2, TNFα2 and IL12) and T helper 2 (Th2) cytokines (IL4/13B1 and IL4/13B2), cytokine and chemokine receptors and the antimicrobial peptide cathelicidin-1 but had limited effects on T helper 17 cytokines and TGFβ1 in PBL. They could also enhance PBL phagocytosis. These results suggest, for the first time in fish, that IL-2 isoforms may have an important role in regulating Th1 and Th2 cell development, and innate and adaptive host defenses in fish, and shed light on lineage-specific expansion, evolution, and functional diversification of IL2 in vertebrates.

Elderly people are at high risk for influenza-related morbidity and mortality due to progressive immunosenescence. While toll-like receptor (TLR) agonist containing adjuvants, and other adjuvants, have been shown to enhance influenza vaccine-induced protective responses, the mechanisms underlying how these adjuvanted vaccines could benefit the elderly remain elusive. Here, we show that a split H1N1 influenza vaccine (sH1N1) combined with a TLR4 agonist, glucopyranosyl lipid adjuvant formulated in a stable oil-in-water emulsion (GLA-SE), boosts IgG2c:IgG1 ratios, enhances hemagglutination inhibition (HAI) titers, and increases protection in aged mice. We find that all adjuvanted sH1N1 vaccines tested were able to protect both young and aged mice from lethal A/H1N1/California/4/2009 virus challenge after two immunizations compared to vaccine alone. We show that GLA-SE combined with sH1N1, however, also provides enhanced protection from morbidity in aged mice given one immunization (based on change in weight percentage). While the GLA-SE-adjuvanted sH1N1 vaccine promotes the generation of cytokine-producing T helper 1 cells, germinal center B cells, and long-lived bone marrow plasma cells in young mice, these responses were muted in aged mice. Differential in vitro responses, dependent on age, were also observed from mouse-derived bone marrow-derived dendritic cells and lung homogenates following stimulation with adjuvants, including GLA-SE. Besides enhanced HAI titers, additional protective factors elicited with sH1N1 + GLA-SE in young mice were observed, including (a) rapid reduction of viral titers in the lung, (b) prevention of excessive lung inflammation, and (c) homeostatic maintenance of alveolar macrophages (AMs) following H1N1 infection. Collectively, our results provide insight into mechanisms of adjuvant-mediated immune protection in the young and elderly.

Mammalian interleukin (IL)-2 is a cytokine centrally involved in the differentiation and survival of CD4+ T helper subsets and CD4+ T regulatory cells and in activation of cytotoxic effector lymphocytes. In bony fish, IL2 orthologs have been identified with an additional divergent IL2-Like gene on the same locus present in several fish species. We report here two divergent IL2 paralogs, IL2A and IL2B, in salmonids that originated from the whole genome duplication event in this fish lineage. The salmonid IL2 paralogs differ not only in sequence but also in exon sizes. The IL-2 isoforms that are encoded have disparate pI values and may have evolved to preferentially bind specific IL-2 receptors. Rainbow trout IL2 paralogs are highly expressed in thymus, spleen, gills, kidney and intestine, important tissues/organs in fish T cell development and function. Their expression in peripheral blood leukocytes (PBL) is low constitutively but can be upregulated by the mixed leukocyte reaction, by the T cell mitogen phytohemagglutinin and by signal mimics of T cell activation (phorbol 12-myristate 13-acetate and calcium ionophore). Both trout IL-2 isoforms promoted PBL proliferation and sustained high-level expression of CD4 and CD8, suggesting that trout IL-2 isoforms are T cell growth/survival factors mainly expressed by activated T cells. The recombinant proteins for these two trout IL2 paralogs have been produced in E. coli and possess shared but also distinct bioactivities. IL-2A, but not IL-2B, induced IL12P35A1 and CXCR1 expression in PBL. IL-2B had a stronger effect on upregulation of the T helper 1 (Th1) cytokine interferon-γ (IFNγ) and could sustain CD8α and CD8β expression levels. Nevertheless, both cytokines upregulated key Th1 (IFNγ1, IFNγ2, TNFα2 and IL12) and T helper 2 (Th2) cytokines (IL4/13B1 and IL4/13B2), cytokine and chemokine receptors and the antimicrobial peptide cathelicidin-1 but had limited effects on T helper 17 cytokines and TGFβ1 in PBL. They could also enhance PBL phagocytosis. These results suggest, for the first time in fish, that IL-2 isoforms may have an important role in regulating Th1 and Th2 cell development, and innate and adaptive host defenses in fish, and shed light on lineage-specific expansion, evolution, and functional diversification of IL2 in vertebrates. [ABSTRACT FROM AUTHOR]

Myasthenia gravis (MG) is an autoimmune neurological disease that is characterized by the expression of anti‑acetylcholine receptor (AChR) antibodies. The immune response at AChRs of neuromuscular junction is disrupted in patients with MG, which manifests as skeletal muscle fatigue and is aggravated following periods of activity and alleviated following rest. Although a novel immune suppressant FTY720 drug, which exhibits strong immune suppression efficacy and minor adverse effects, is available, its role and mechanism in MG have not been elucidated. The aim of this study was to investigate the role of FTY720 in MG. A total of 60 healthy female Lewis rats were randomly assigned into 4 groups: Control group, Model group of experimental autoimmune myasthenia gravis (EAMG), 0.5 mg/kg FTY720‑treatment EAMG group and 1.0 mg/kg FTY720‑treatment EAMG group. Body weight and symptoms were examined; Lennon score was used to evaluate improvement of clinical symptoms. Reverse transcription‑quantitative polymerase chain reaction and ELISA were used to test the mRNA and protein expression levels, respectively, of the helper T (Th)1 and Th2 cell cytokines, including interleukin (IL)‑2, interferon (IFN)‑γ, IL‑4 and IL‑6 in thymus tissue and serum. FTY720 treatment improved rat MG symptoms, increased body weight and decreased Lennon score. FTY720 treatments also reduced tissue and serum levels of IL‑2, IFN‑γ and IL‑6, but not IL‑4 expression levels. FTY720 suppressed the inflammatory response and improved EAMG symptoms by inhibiting the secretion of inflammatory factors. [ABSTRACT FROM AUTHOR]

T-bet refer to the transcription factor for T helper 1 (Th1) cell differentiation from naive Th precursor cells. It is highly expressed in type 1 immune cells such as Th1, NK and NKT. To assess T-bet expression in 30 Urinary bladder carcinoma biopsy (UBC) and 10 benign tumor (BT) control cases using immunohistochemistry. T-bet expression was assessed by using immunohistochemistry in tissues specimens. Immunostaining results showed that theexpression of T-bet was elevated in patient with Bladder cancer compare to benign control (24/30 (80%), 4/10(40%), respectively with significantly difference (p≤0. 05), and its expression was strongly positive and elevated in bladder cancer patients investigated with high-grade compared to the bladder cancer patients investigated with low-grade. Also, the expression of T-bet was significantly higher in advance stages or invasive (T2 ≥), than the superficial bladder tumors (T2 ≤) (p ≤ 0. 05). The current data proposed that the expressionof T-bet may be associated with high clinico pathological stages and grades in bladder cancer tissues for Iraqi patients. [ABSTRACT FROM AUTHOR]

Elderly people are at high risk for influenza-related morbidity and mortality due to progressive immunosenescence. While toll-like receptor (TLR) agonist containing adjuvants, and other adjuvants, have been shown to enhance influenza vaccine-induced protective responses, the mechanisms underlying how these adjuvanted vaccines could benefit the elderly remain elusive. Here, we show that a split H1N1 influenza vaccine (sH1N1) combined with a TLR4 agonist, glucopyranosyl lipid adjuvant formulated in a stable oil-in-water emulsion (GLA-SE), boosts IgG2c:IgG1 ratios, enhances hemagglutination inhibition (HAI) titers, and increases protection in aged mice. We find that all adjuvanted sH1N1 vaccines tested were able to protect both young and aged mice from lethal A/ H1N1/California/4/2009 virus challenge after two immunizations compared to vaccine alone. We show that GLA-SE combined with sH1N1, however, also provides enhanced protection from morbidity in aged mice given one immunization (based on change in weight percentage). While the GLA-SE-adjuvanted sH1N1 vaccine promotes the generation of cytokine-producing T helper 1 cells, germinal center B cells, and long-lived bone marrow plasma cells in young mice, these responses were muted in aged mice. Differential in vitro responses, dependent on age, were also observed from mouse-derived bone marrow-derived dendritic cells and lung homogenates following stimulation with adjuvants, including GLA-SE. Besides enhanced HAI titers, additional protective factors elicited with sH1N1 + GLA-SE in young mice were observed, including (a) rapid reduction of viral titers in the lung, (b) prevention of excessive lung inflammation, and (c) homeostatic maintenance of alveolar macrophages (AMs) following H1N1 infection. Collectively, our results provide insight into mechanisms of adjuvant-mediated immune protection in the young and elderly. [ABSTRACT FROM AUTHOR]

Curcumin is a polyphenol natural product isolated from turmeric, interacting with different cellular and molecular targets and, consequently, showing a wide range of pharmacological effects. Recent preclinical and clinical trials have revealed immunomodulatory properties of curcumin that arise from its effects on immune cells and mediators involved in the immune response, such as various T-lymphocyte subsets and dendritic cells, as well as different inflammatory cytokines. Systemic lupus erythematosus (SLE) is an inflammatory, chronic autoimmune-mediated disease characterized by the presence of autoantibodies, deposition of immune complexes in various organs, recruitment of autoreactive and inflammatory T cells, and excessive levels of plasma proinflammatory cytokines. The function and numbers of dendritic cells and T cell subsets, such as T helper 1 (Th1), Th17, and regulatory T cells have been found to be significantly altered in SLE. In the present report, we reviewed the results of in vitro , experimental (pre-clinical), and clinical studies pertaining to the modulatory effects that curcumin produces on the function and numbers of dendritic cells and T cell subsets, as well as relevant cytokines that participate in SLE. [ABSTRACT FROM AUTHOR]

Loss of oral tolerance (LOT) to gluten, driven by dendritic cell (DC) priming of gluten-specific T helper 1 (Th1) cell immune responses, is a hallmark of celiac disease (CeD) and can be triggered by enteric viral infections. Whether certain commensals can moderate virus-mediated LOT remains elusive. Here, using a mouse model of virus-mediated LOT, we discovered that the gut-colonizing protist Tritrichomonas (T.) arnold promotes oral tolerance and protects against reovirus- and murine norovirus-mediated LOT, independent of the microbiota. Protection was not attributable to antiviral host responses or T. arnold -mediated innate type 2 immunity. Mechanistically, T. arnold directly restrained the proinflammatory program in dietary antigen-presenting DCs, subsequently limiting Th1 and promoting regulatory T cell responses. Finally, analysis of fecal microbiomes showed that T. arnold- related Parabasalid strains are underrepresented in human CeD patients. Altogether, these findings will motivate further exploration of oral-tolerance-promoting protists in CeD and other immune-mediated food sensitivities. [Display omitted] • T. arnold promotes oral tolerance and protects against virus-mediated LOT • T. arnold -mediated protection is independent of antiviral immunity and the microbiota • Succinate and IL-25 are not sufficient to protect against virus-mediated LOT • T. arnold restrains virus-induced IRF1/NF-κB inflammatory responses in cDC1 Enteric viruses can trigger loss of oral tolerance to dietary gluten, resulting in the development of celiac disease. Medina Sanchez et al. discovered Tritrichomonas arnold , a previously undescribed murine gut commensal protist capable of preventing virus-mediated loss of oral tolerance by directly restraining proinflammatory dendritic cell function. [ABSTRACT FROM AUTHOR]

NLRP10 is a nucleotide-binding oligomerization domain-like receptor that functions as an intracellular pattern recognition receptor for microbial products. Here, we generated a Nlrp10−/− mouse to delineate the role of NLRP10 in the host immune response and found that Nlrp10−/− dendritic cells (DCs) elicited sub-optimal IFNγ production by antigen-specific CD4+ T cells compared to wild-type (WT) DCs. In response to T-cell encounter, CD40 ligation or Toll-like receptor 9 stimulation, Nlrp10−/− DCs produced low levels of IL-12, due to a substantial decrease in NF-κB activation. Defective IL-12 production was also evident in vivo and affected IFNγ production by CD4+ T cells. Upon Mycobacterium tuberculosis (Mtb) infection, Nlrp10−/− mice displayed diminished T helper 1-cell responses and increased bacterial growth compared to WT mice. These data indicate that NLRP10-mediated IL-12 production by DCs is critical for IFNγ induction in T cells and contributes to promote the host defense against Mtb.

Experimental infection with the protozoan parasite Leishmania major has been extensively used to understand the mechanisms involved in T helper cell differentiation. Following infection, C57BL/6 mice develop a small self-healing cutaneous lesion and they are able to control parasite burden, a process linked to the development of T helper (Th) 1 cells. The local presence of IL-12 has been reported to be critical in driving Th1 cell differentiation. In addition, the early secretion of IL-4 was reported to potentially contribute to Th1 cell differentiation. Following infection with L. major, early keratinocyte-derived IL-4 was suggested to contribute to Th1 cell differentiation. To investigate a putative autocrine role of IL-4 signaling on keratinocytes at the site of infection, we generated C57BL/6 mice deficient for IL-4Rα expression selectively in keratinocytes. Upon infection with L. major, these mice could control their inflammatory lesion and parasite load correlating with the development of Th1 effector cells. These data demonstrate that IL-4 signaling on keratinocytes does not contribute to Th1 cell differentiation. To further investigate the source of IL-4 in the skin during the first days after L. major infection, we used C57BL/6 IL-4 reporter mice allowing the visualization of IL-4 mRNA expression and protein production. These mice were infected with L. major. During the first 3 days after infection, skin IL-4 mRNA expression was observed selectively in mast cells. However, no IL-4 protein production was detectable locally. In addition, early IL-4 blockade locally had no impact on subsequent Th1 cell differentiation and control of the disease. Taken together, the present data rule out a major role for skin IL-4 and keratinocyte IL-4Rα signaling in the development of a Th1 protective immune response following experimental infection with L. major.

Background: Cytokines produced by different subsets of T cells are the key mediators to adjust the quality of immune responses. Despite evidence of induction of an immune reaction against tumors such as breast cancer, not all responses are protective. In this study we attempt to evaluate the expression profile of several cytokines from the T helper 1 and 2 subsets in blood cells from patients with breast cancer. Methods:We recruited 100 recently diagnosed patients with confirmed pathological reports. Peripheral blood samples were taken and the expression of the transcripts for IL-2, IL-12A, IL-12B, IFN-γ, IL-4, IL-10, IL-13 and IL-13Rα2 were measured by quantitative real time PCR. We correlated the results to clinical findings and compared the results to those from 64 healthy individuals. Results: Among the studied cytokines, we observed a significant increase in the expression of T helper 1 pro-inflammatory cytokines IL-12B, IL-2 and IFN-γ compared to healthy controls. Elevated expression of those cytokines was associated with high stage and/or high grade tumors but there was no association with other clinical determinants. Simultaneously, blood cells showed high expression of IL-10, but not the other studied T helper 2 cytokines. Conclusion: The mixed and complex cytokine profile of T helper 1 and 2 immunity in blood cells may show an immunological imbalance which makes the overall system favor cancer. This may be a potential target for immunotherapy approaches, however more comprehensive results are needed.

NLRP10 is a nucleotide-binding oligomerization domain-like receptor that functions as an intracellular pattern recognition receptor for microbial products. Here, we generated a Nlrp10-/- mouse to delineate the role of NLRP10 in the host immune response and found that Nlrp10-/- dendritic cells (DCs) elicited sub-optimal IFNγ production by antigen- specific CD4+ T cells compared to wild-type (WT) DCs. In response to T-cell encounter, CD40 ligation or Toll-like receptor 9 stimulation, Nlrp10-/- DCs produced low levels of IL-12, due to a substantial decrease in NF-κB activation. Defective IL-12 production was also evident in vivo and affected IFNγ production by CD4+ T cells. Upon Mycobacterium tuberculosis (Mtb) infection, Nlrp10-/- mice displayed diminished T helper 1-cell responses and increased bacterial growth compared to WT mice. These data indicate that NLRP10-mediated IL-12 production by DCs is critical for IFNγ induction in T cells and contributes to promote the host defense against Mtb. [ABSTRACT FROM AUTHOR]

Experimental infection with the protozoan parasite Leishmania major has been extensively used to understand the mechanisms involved in T helper cell differentiation. Following infection, C57BL/6 mice develop a small self-healing cutaneous lesion and they are able to control parasite burden, a process linked to the development of T helper (Th) 1 cells. The local presence of IL-12 has been reported to be critical in driving Th1 cell differentiation. In addition, the early secretion of IL-4 was reported to potentially contribute to Th1 cell differentiation. Following infection with L. major, early keratinocyte-derived IL-4 was suggested to contribute to Th1 cell differentiation. To investigate a putative autocrine role of IL-4 signaling on keratinocytes at the site of infection, we generated C57BL/6 mice deficient for IL-4Rα expression selectively in keratinocytes. Upon infection with L. major, these mice could control their inflammatory lesion and parasite load correlating with the development of Th1 effector cells. These data demonstrate that IL-4 signaling on keratinocytes does not contribute to Th1 cell differentiation. To further investigate the source of IL-4 in the skin during the first days after L. major infection, we used C57BL/6 IL-4 reporter mice allowing the visualization of IL-4 mRNA expression and protein production. These mice were infected with L. major. During the first 3 days after infection, skin IL-4 mRNA expression was observed selectively in mast cells. However, no IL-4 protein production was detectable locally. In addition, early IL-4 blockade locally had no impact on subsequent Th1 cell differentiation and control of the disease. Taken together, the present data rule out a major role for skin IL-4 and keratinocyte IL-4Rα signaling in the development of a Th1 protective immune response following experimental infection with L. major. [ABSTRACT FROM AUTHOR]

Exercise (with appropriate intensity and duration) is a natural modulator of immune responses and may be useful to increase the vaccine response towards antigen. According to the fact that rural area responding butter than urbon area to vaccine protocol, this study was undertaken to test the hypothesis that short term exercise training as an adjuvant for antigen such as herpes simplex virus type 1 (HSV-1) in animal models. Mice with/without access to short term exercise training were immunized intramuscularly with inactivated KOS strain of HSV-1. Immune responses was investigated with regards of both cell-mediated and humoral immunity. In this study by using short term exercise training as an adjuvant enhanced Th1 response while it did not show significant effect on Th2 responses towards HSV-1 immunization. Also, immunoglobulin G (IgG) 2a/IgG1-ratios increased in vaccine with short term exercise training group. These results suggested that coupling short term moderate exercise training as a mild adjuvant with vaccination may enhance cell-mediated immune responses especially Th1 responses. [ABSTRACT FROM AUTHOR]

Neonatal Bacillus Calmette-Guérin (BCG) vaccination results in a positive effect on hippocampal neurogenesis and cognition. Serum cytokines are considered to be the chief culprit. In this study, serum from BCG-treated mice was identified as Th1 polarized serum. The serum showed an increased ratio of IFN-γ to IL-4 and decreased levels of TNF-α and IL-6. After Th1 polarized serum was injected intraperitoneally into postnatal mice, the levels of cytokines and ratio of IFN-γ to IL-4 in the serum and hippocampus of postnatal mice showed a similar alteration as those in Th1 polarized serum. This result indicated that the immune homeostatic milieu in postnatal mice was broken and the Th1 polarized systemic environment in the BCG-serum group was remodeled. The BCG-serum group displayed more BrdU + /DCX + cells, BrdU + /NeuN + cells, Nestin + cells and better cognitive abilities. In neural stem cells, the Wnt7a/β-catenin signaling pathway was activated and exposure to the Wnt7a antagonist Dickkopf-1 inhibited BCG-serum-induced Wnt7a/β-catenin signaling, neurogenesis and cognitive function. Additionally, BCG-serum was associated with elevations in hippocampal brain-derived neurotrophic factor (BDNF) levels, and BDNF expression in the BCG-serum group was offset by Dickkopf-1 treatment. By rebalancing the Th1 polarized systemic environment in neonatal mice, it is possible that treatment with BCG-serum promotes hippocampal neurogenesis and improves cognitive functions, which are associated with Wnt7a/β-catenin-BDNF signaling. [ABSTRACT FROM AUTHOR]

Interferon gamma (IFN-γ) signaling in T cells plays an important role in developing T helper 1 (Th1)-mediated inflammation. Selective regulation of IFN-γ signaling is an attractive strategy for treating Th1-mediated immune diseases. In this study, we aimed to explore possible means of targeting IFN-γ signaling by using small molecule compound. A synthetic small molecule FC9 was identified as it selectively inhibited IFN-γ signaling in T cells without suppressing interleukin 4 (IL-4) signaling. Furthermore, FC9 inhibited IFN-γ-induced Janus kinase 2 (JAK2) activation via competing with IFN-γ for binding to IFN-γ receptor 1 (IFN-γ R1). Interestingly, we found that FC9 bound to IFN-γ R1 and selectively suppressed Th1 but not Th2 immune response in T cells, resulting in an improvement in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. In conclusion, FC9-induced competitive blockade of IFN-γ R1 for selective inhibition of IFN-γ signaling, demonstrated a novel mean of targeting IFN-γ signaling. These findings could lead to increased options for the treatment of Crohn’s disease and other Th1-mediated inflammatory diseases. [ABSTRACT FROM AUTHOR]

A pre-designed plasmid containing the gene encoding the second subunit of Echinococcus granulosus AgB8 (EgAgB8/2) was used to study the effect of the immunization route on the immune response in BALB/c mice. Mice were immunized with pDRIVEEgAgB8/ 2 or pDRIVE empty cassette using the intramuscular (i.m.), intranasal (i.n.) or the epidermal gene gun (g.g.) routes. Analysis of the antibody response and cytokine data revealed that gene immunization by the i.m. route induced a marked bias towards a T helper type 1 (Th1) immune response as characterized by high IFN-γ gene expression and a low IgG1/IgG2a reactivity index (R.I.) ratio of 0.04. The i.n. route showed a moderate IFN-γ expression but a higher IgG1/IgG2a R.I. ratio of 0.25 indicating a moderate Th1 response. In contrast, epidermal g.g. immunization induced a Th2 response characterized by high IL-4 expression and the highest IgG1/IgG2a R.I. ratio of 0.58. In conclusion, this study showed the advantage of genetic immunization using the i.m. route and i.n. over the epidermal g.g. routes in the induction of Th1 immunity in response to E. granulosus AgB gene immunization.

T helper 1 (Th1) type cytokines and chemokines are bioactive mediators in inflammation underling several diseases and co-morbid conditions, such as cardiovascular and metabolic disorders. Th1 chemokine CXCL10 participates in heart damage initiation/progression; cardioprotection has been recently associated with sildenafil, a type 5 phosphodiesterase inhibitor. We aimed to evaluate the effect of sildenafil on CXCL10 in inflammatory conditions associated with diabetic cardiomyopathy. We analyzed: CXCL10 gene and protein in human cardiac, endothelial, and immune cells challenged by pro-inflammatory stimuli with and without sildenafil; serum CXCL10 in diabetic subjects at cardiomyopathy onset, before and after 3 months of treatment with sildenafil vs. placebo. Sildenafil significantly decreased CXCL10 protein secretion (IC = 2.6 × 10) and gene expression in human cardiomyocytes and significantly decreased circulating CXCL10 in subjects with chemokine basal level ≥ 930 pg/ml, the cut-off value as assessed by ROC analysis. In conclusion, sildenafil could be a pharmacologic tool to control CXCL10-associated inflammation in diabetic cardiomyopathy. [ABSTRACT FROM AUTHOR]

The discovery of effective adjuvants for many vaccines especially those with limited commercial appeal, such as vaccines to poverty-related diseases, is required. In this work, we demonstrated that subcutaneous co-administration of mice with the outer membrane protein U-Omp19 from Brucella spp. plus OVA as antigen (Ag) increases Ag-specific T cell proliferation and T helper (Th) 1 immune responses in vitro and in vivo . U-Omp19 treated dendritic cells promote IFN-γ production by specific CD4 + T cells and increases T cell proliferation. U-Omp19 co-administration induces the production of Ag specific effector memory T cell populations (CD4 + CD44 high CD62L low T cells). Finally, subcutaneous co-administration of U-Omp19 with Trypanosoma cruzi Ags confers protection against virulent parasite challenge, reducing parasitemia and weight loss while increasing mice survival. These results indicate that the bacterial protein U-Omp19 when delivered subcutaneously could be a suitable component of vaccine formulations against infectious diseases requiring Th1 immune responses. [ABSTRACT FROM AUTHOR]

Objective: To investigate the expression of interleukin-21 (IL-21) and its correlation to T-cell subpopulation including Th1, Tc1 and Th17 cells in Ulcerative colitis (UC). Material and methods: We examined the expression of IL-21, IL-17 and IFN-γ in UC patients and controls by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Results: We found that IL-21 was expressed on CD3+CD8-T cells by flow cytometry. Plasma IL-21 level and the percentage of CD3+CD8-IL-21+ T cells were significantly elevated in UC patients compared to controls. The percentage of CD3+CD8-IL-17+ T (Th17), CD3+CD8-IFN-γ+ T (Th1) and CD3+CD8+ IFN-γ+ T (Tc1) cells was also significantly increased in UC patients. Moreover, we found a significant positive correlation between CD3+CD8-IL-21+T cells and Th17 cells. Conclusions: Elevated IL-21 and its positive correlation to Th17 cells may play a role in the pathogenesis of UC. [ABSTRACT FROM AUTHOR]

Progressive multiple sclerosis (MS) is an immune-mediated demyelinating disease in which both imbalanced T helper (Th) subsets and aberrant cytokine profiles have been found. Interleukin-27 (IL-27), a cytokine with pro-inflammatory and anti-inflammatory effects, plays pleiotropic roles in immunomodulation. In the present study, plasma levels of IL-27, interferon-gamma (IFN-γ), IL-17 and frequencies of peripheral Th1, Th17 cells were determined by enzyme-linked immunosorbent assay (ELISA) and flow cytometry in 45 progressive MS and 25 healthy controls. mRNA expression levels of IL-27, IFN-γ, T-bet, IL-17 and RAR-related orphan receptor gamma t (RORγt) in peripheral blood mononuclear cells (PBMCs) were also quantified by real-time polymerase chain reaction. Plasma and mRNA levels of IL-27 in progressive MS patients were significantly lower than those in healthy controls, while plasma concentrations of IL-17, frequencies of circulating Th17, and mRNA expression levels of IL-17 as well as RORγt were all increased remarkably compared with healthy controls. No statistical significance was observed in IFN-γ and T-bet mRNA expression or plasma IFN-γ levels between progressive MS patients and healthy controls. Moreover, plasma levels of IL-27 were found to be negatively correlated to the percentages of circulating Th17 or plasma IL-17 concentrations in patients with progressive MS. Our data showed that progressive MS patients had decreased plasma and mRNA expression levels of IL-27, suggesting that it might be involved in the pathophysiological process of MS. [ABSTRACT FROM AUTHOR]