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Background: Asthma pathology may induce changes in naïve/memory lymphocyte proportions assessable through the evaluation of surface CD26 (dipeptidyl peptidase 4/DPP4) levels. Our aim was to investigate the association of asthma phenotype/severity with the relative frequency of CD26−/lo, CD26int and CD26hi subsets within different lymphocyte populations. Methods: The proportion of CD26−/lo, CD26int and CD26hi subsets within CD4+ effector T cells (Teff), total CD4− lymphocytes, γδ‐T cells, NK cells and NKT cells was measured in peripheral blood samples from healthy (N = 30) and asthma (N = 119) donors with different phenotypes/severities by flow cytometry. We performed K‐means clustering analysis and further characterised the CD4+CD26−/lo Teff cell subset by LC–MS/MS and immunofluorescence. Results: Cluster analysis including clinical and flow cytometry data resulted in four groups, two of them with opposite inflammatory profiles (neutrophilic vs. eosinophilic). Neutrophilic asthma presented reduced CD4−CD26hi cells, which negatively correlated with systemic inflammation. Eosinophilic asthma displayed a general expansion of CD26−/lo subsets. Specifically, CD4+CD26−/lo Teff expansion was confirmed in asthma, especially in atopic patients. Proteomic characterisation of this subset with a TEM/TEMRA phenotype revealed upregulated levels of innate (e.g. MPO and RNASE2) and cytoskeleton/extracellular matrix (e.g. MMP9 and ACTN1) proteins. Immunofluorescence assays confirmed the presence of atypical proteins for CD4+ T cells, and an enrichment in 'flower‐like' nuclei and MMP9/RNASE2 levels in CD4+CD26−/lo Teff compared to CD4+ T lymphocytes. Conclusion: There is an association between CD26 levels in different lymphocyte subsets and asthma phenotype/severity. CD4+CD26−/loTEMRA cells expressing innate proteins specific to eosinophils/neutrophils could be determinant in sustaining long‐term inflammation in adult allergic asthma. [ABSTRACT FROM AUTHOR]

Background: Asthma pathology may induce changes in naïve/memory lymphocyte proportions assessable through the evaluation of surface CD26 (dipeptidyl peptidase 4/DPP4) levels. Our aim was to investigate the association of asthma phenotype/severity with the relative frequency of CD26 -/lo , CD26 int and CD26 hi subsets within different lymphocyte populations., Methods: The proportion of CD26 -/lo , CD26 int and CD26 hi subsets within CD4 + effector T cells (T eff ), total CD4 - lymphocytes, γδ-T cells, NK cells and NKT cells was measured in peripheral blood samples from healthy (N = 30) and asthma (N = 119) donors with different phenotypes/severities by flow cytometry. We performed K-means clustering analysis and further characterised the CD4 + CD26 -/lo T eff cell subset by LC-MS/MS and immunofluorescence., Results: Cluster analysis including clinical and flow cytometry data resulted in four groups, two of them with opposite inflammatory profiles (neutrophilic vs. eosinophilic). Neutrophilic asthma presented reduced CD4 - CD26 hi cells, which negatively correlated with systemic inflammation. Eosinophilic asthma displayed a general expansion of CD26 -/lo subsets. Specifically, CD4 + CD26 -/lo T eff expansion was confirmed in asthma, especially in atopic patients. Proteomic characterisation of this subset with a T EM /T EMRA phenotype revealed upregulated levels of innate (e.g. MPO and RNASE2) and cytoskeleton/extracellular matrix (e.g. MMP9 and ACTN1) proteins. Immunofluorescence assays confirmed the presence of atypical proteins for CD4 + T cells, and an enrichment in 'flower-like' nuclei and MMP9/RNASE2 levels in CD4 + CD26 -/lo T eff compared to CD4 + T lymphocytes., Conclusion: There is an association between CD26 levels in different lymphocyte subsets and asthma phenotype/severity. CD4 + CD26 -/lo T EMRA cells expressing innate proteins specific to eosinophils/neutrophils could be determinant in sustaining long-term inflammation in adult allergic asthma., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Summary: Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase (NOS) inhibitor/uncoupler inducing vascular pathology. Vascular pathology is an important factor for the development and progression of CNS pathology of MS, yet the role of ADMA in MS remains elusive. Patients with multiple sclerosis (MS) are reported to have elevated blood levels of ADMA, and mice with experimental autoimmune encephalomyelitis (EAE, an animal model of MS) generated by auto‐immunization of myelin oligodendrocyte glycoprotein (MOG) and blood–brain barrier (BBB) disruption by pertussis toxin also had increased blood ADMA levels in parallel with induction of clinical disease. To explore the role of ADMA in EAE pathogenesis, EAE mice were treated with a daily dose of ADMA. It is of special interest that ADMA treatment enhanced the BBB disruption in EAE mice and exacerbated the clinical and CNS disease of EAE. ADMA treatment also induced the BBB disruption and EAE disease in MOG‐immunized mice even without pertussis toxin treatment, suggesting the role of ADMA in BBB dysfunction in EAE. T‐cell polarization studies also documented that ADMA treatment promotes TH1‐ and TH17‐mediated immune responses but without affecting Treg‐mediated immune response in EAE mice as well as in in vitro T‐cell culture. Taken together, these data, for the first time, document the vascular and immunopathogenic roles of ADMA in EAE, thus pointing to the potential of ADMA‐mediated mechanism as a new target of potential therapy for MS. [ABSTRACT FROM AUTHOR]

In classical Hodgkin lymphoma (cHL), the significance of the interplay between Hodgkin and Reed–Sternberg cells (HRS) and reactive T cells remains poorly defined. By immunohistochemistry on bioptic cHL specimens, we found that HRS and surrounding T lymphocytes stained positive for IL-17 in 40% of cases. IL-17 was detectable in a similar proportion of patients' sera and correlated with disease burden. Supernatants of KM-H2 and HDLM-2 cHL cell lines guided preferential chemotaxis of CCR6+ T lymphocytes. Coculture of cHL cell lines with PBMC promoted the enrichment of Th17 lymphocytes and Foxp3+/IL-17+ cells, whereas T regulatory cells slightly decreased. Soluble CD30 downmodulated membrane CD30 expression on T cells and contributed to their polarization shift by stimulating IL-17 production and reducing IFN-γ synthesis. Thus, HRS and a number of reactive CD4+ T cells, attracted by tumor-secreted chemokines, produce an IL-17 tumor-shaped inflammatory milieu in a cHL subset. [ABSTRACT FROM AUTHOR]

Interleukin-4 (IL-4) intervenes essential pro-inflammatory functions in asthma including enlistment of the IgE isotype switch, expression of vascular cell adhesion molecule-1 (VCAM-1), advancement of eosinophil transmigration crosswise over endothelium, mucus secretion and differentiation of T helper type 2 lymphocytes leading to cytokine release. Asthma is a complex hereditary confusion that has been connected to polymorphisms in theIL-4 gene promoter and proteins involved in IL-4 signaling. Soluble recombinant IL-4 receptor needs transmembrane and cytoplasmic initiating spaces and can in this manner sequester IL-4 without interceding cell actuation. We report the consequences of beginning clinical preliminaries, which show clinical viability of this normally happening IL-4 rival as a remedial specialist in asthma. In asthmatic case lower number of physical dynamic people was viewed when contrasted with control (41.57% Vs 53.33 %) a noteworthy relationship of physical movement was seen (Chi square esteem 5.524, df-1 and P esteem 0.0188). Bidi and cigarette smokers were incorporated as smoking populace. The information shows the level of smokers was not particularly extraordinary between both in the event that and control populace (25.79% Vs 22.38%) and no noteworthy contrast was seen. Information from polymorphic screening, Non-huge dimension of progress has been seen in dispersion of IL-4 genotypes in Healthy Control (HC) amass when contrasted with asthmatic patients gathering in spite of the fact that HC group indicated little increment in like manner 'B1/B1' genotype when contrasted with Patients of asthma(5.62% versus 5.3% individually) yet contrast was difference was nominal and statistically non- significant. Likewise, 'B2/B2' genotype was available at lesser recurrence in asthmatic patients aggregate 51.9% and furthermore in charge gather 54.2%. The general genotype was measurably non-significant (χ2 =0.1918, P=0.9086) however 'B1/B1' genotype recurrence was higher in control gathering and might be defensive in our populace. [ABSTRACT FROM AUTHOR]

We previously reported that S-nitrosoglutathione (GSNO), an endogenous nitric oxide carrier, attenuated T H 17-mediated immune responses in experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS). Cellular GSNO homeostasis is regulated via its synthesis by reaction between nitric oxide and glutathione and its enzymatic catabolism by GSNO reductase (GSNOR). In this study, we evaluated potential of reversible inhibitor of GSNOR (N6022) in comparison with exogenous GSNO in immunopathogenesis of EAE. Daily treatment of EAE mice with N6022 or exogenous GSNO significantly attenuated the clinical disease of EAE, but N6022 treatment showed greater efficacy than GSNO. Both N6022 and exogenous GSNO treatments increased the spleen levels of GSNO, as documented by increased protein-associated S-nitrosothiols, and inhibited polarization and CNS effector function of proinflammatory T H 17 cells while inducing the polarization and CNS effector function of anti-inflammatory CD4 + CD25 + FOXP3 - regulatory T (Treg) cells. Moreover, N6022 further attenuated T H 1 while inducing T H 2 and CD4 + CD25 + FOXP3 + Treg in their polarization and CNS effector functions. Similar to GSNO, the N6022 treatment protected against the EAE disease induced demyelination. However, neither exogenous GSNO nor N6022 treatment did not cause significant systemic lymphopenic effect as compared to FTY720. Taken together, these data document that optimization of cellular GSNO homeostasis by GSNOR inhibitor (N6022) in NO metabolizing cells attenuates EAE disease via selective inhibition of pro-inflammatory subsets of CD4 + cells (T H 1/T H 17) while upregulating anti-inflammatory subsets of CD4 + cells (T H 2/Treg) without causing lymphopenic effects and thus offers a potential treatment option for MS/EAE. [ABSTRACT FROM AUTHOR]

An immunophenotyping analysis was performed in peripheral blood samples from seven patients with lung cancer unfit for surgery treated with stereotactic body radiotherapy (SBRT). The objective was to characterize the effect of SBRT on the host immune system. Four patients received 60 Gy (7.5 Gy × 8) and three 50 Gy (12.5 Gy × 4). Analyses were performed before SBRT, 72 h after SBRT, and at one, three, and six months after the end of SBRT. Of note, there was a specific increase of the immunoactive component of the immune system, with elevation of CD56+highCD16+ natural killer (NK) cells (0.95% at baseline to 1.38% at six months), and a decrease of the immunosuppressive component of the immune system, with decreases of CD4+CD25+Foxp3+CDA5RA− regulatory T cells (4.97% at baseline to 4.46% at six months), granulocytic myeloid-derived suppressor cells (G-MDSCs) (from 66.1% at baseline to 62.6% at six months) and monocytic (Mo-MDSCs) (8.2% at baseline to 6.2% at six months). These changes were already apparent at 72 h and persisted over six months. SBRT showed an effect on systemic immune cell populations, which is a relevant finding for supporting future combinations of SBRT with immunotherapy for treating lung cancer patients.

Purpose of Review: The adaptive immune response orchestrated by type 2 T helper (Th2) lymphocytes, strictly cooperates with the innate response of group 2 innate lymphoid cells (ILC2), in the protection from helminths infection, as well as in the pathogenesis of allergic disease. The aim of this review is to explore the pathogenic role of ILC2 in different type 2-mediated disorders. Recent Findings: Recent studies have shown that epithelial cell-derived cytokines and their responding cells, ILC2, play a pathogenic role in bronchial asthma, chronic rhinosinusitis, and atopic dermatitis. Summary: The growing evidences of the contribution of ILC2 in the induction and maintenance of allergic inflammation in such disease suggest the possibility to target them in therapy. Biological therapies blocking ILC2 activation or neutralizing their effector cytokines are currently under evaluation to be used in patients with type 2-dominated diseases. [ABSTRACT FROM AUTHOR]

Abstract Interleukin-4 (IL-4) mediates important pro-inflammatory functions in asthma including induction of the IgE isotype switch, expression of vascular cell adhesion molecule-1 (VCAM-1), promotion of eosinophil transmigration across endothelium, mucus secretion, and differentiation of T helper type 2 lymphocytes leading to cytokine release. Asthma is a complex genetic disorder that has been linked to polymorphisms in the IL-4 gene promoter and proteins involved in IL-4 signaling. Soluble recombinant IL-4 receptor lacks transmembrane and cytoplasmic activating domains and can therefore sequester IL-4 without mediating cellular activation. We report the results of initial clinical trials, which demonstrate clinical efficacy of this naturally occurring IL-4 antagonist as a therapeutic agent in asthma.

Background: Crohn's disease (CD) and Hidradenitis suppurativa (HS) are both chronic inflammatory diseases. The pathogenesis of these diseases is multifactorial, due to the interaction of genetic and environmental factors leading to a deregulated local immune response where T lymphocytes play a major role. To the best of our knowledge, no previous study has clarified whether the pathogenetic mechanism of perianal CD and HS is the same. We therefore analyzed the cellular expression pattern and the cytokine repertoire in three patients suffering from both perianal CD and HS. Methods: We evaluated three patients affected by concurrent HS and CD with fistulizing perianal disease. Surgical specimens have been fixed and embedded in paraffin prior to sectioning for histological examination. Inflammatory tissue curettages have been recovered during intervention from perianal fistulas and HS lesions in order to analyze the phenotypic and functional characteristics of infiltrating T cells. In particular we evaluated T cells, by flow cytometry, for cytokine production profile and expression of surface markers. Moreover, analysis of the T cell repertoire was performed by means of spectratyping, in only one patient. Results: A higher frequency of CD4+ CD161+ T lymphocytes has been detected in CD fistulas and in HS lesions than in peripheral blood (PB) samples. In the patient in whom we derived enough cells from the three sources, we found higher frequency of CD4+ IL-17- producing cells in HS lesion and fistula lesion compared to PB. It is noteworthy that the same clonotypes were expanded in this patient in T cells derived from both HS lesion and fistula lesion. Conclusion: The presence of numerous CD4+ CD161+ lymphocytes in fistula and HS lesion curettages suggests that these cells may play a pathogenic role, and candidates CD161 as a possible biological target for medical treatment. [ABSTRACT FROM AUTHOR]

Résumé: Bien que l’étiopathogénie de la maladie de Behçet (MB) demeure inexpliquée, de nouvelles données suggèrent que la réaction inflammatoire au cours de la MB résulte d’une perturbation de l’homéostasie de la réponse immunitaire innée et adaptative chez des individus génétiquement prédisposés. Il en découle une activation des lymphocytes T au niveau du sang périphérique et des sites inflammatoires. À ce jour, HLA-B51 demeure le principal facteur de susceptibilité génétique. Les études génomiques récentes ont confirmé cette donnée et ont permis de mettre en évidence de nouveaux gènes de susceptibilité (IL-10, IL-23R, IL-12RB2). Un agent infectieux bactérien pourrait déclencher la maladie par une réponse anormale des cellules T vis-à-vis des HSP (heat shock proteins) bactériennes provoquant secondairement, par réactivité croisée, la prolifération de cellules T auto-réactives vis-à-vis des HSP humaines. Différents agents infectieux ont été étudiés, et il en ressort que Streptococcus sanguis serait l’agent pathogène le plus incriminé. Récemment, il a été démontré un déséquilibre des lymphocytes T consistant en l’expansion des Th1 et Th17 et une diminution des lymphocytes T régulateurs (Treg). Les cytokines de type IL-17, IL-23 et IL-21 jouent un rôle déterminant. Les principales cellules impliquées dans l’inflammation au cours de la MB sont les polynucléaires neutrophiles, les lymphocytes T CD4+ et les cellules cytotoxiques. Enfin, il a été clairement établi qu’une dysfonction de la cellule endothéliale joue un rôle dans la MB. Les progrès réalisés dans la compréhension de la physiopathologie de la MB seront certainement à l’origine de développement de nouvelles thérapeutiques plus efficaces que les traitements disponibles. Dans cette revue, nous avons analysé différents facteurs étiopathogéniques à la lumière des données récentes. [ABSTRACT FROM AUTHOR]

Aim Porphyromonas gingivalis can synthesize an extracellular capsule and different serotypes have been described based on capsular antigenicity. On dendritic cells ( DCs), the type of capsule present plays a role on the strength of the developed immune response. This study aimed to investigate the T-lymphocyte responses when stimulated with autologous mature DCs exposed to different P. gingivalis K-serotypes. Materials and Methods Naïve CD4+T-lymphocytes were obtained from healthy subjects and stimulated with autologous DCs primed with increasing multiplicity of infections of the different P. gingivalis K-serotypes. The Th1, Th2, Th17 and T-regulatory cytokines and transcription factor levels were quantified. Results Distinct types of response were detected when T-lymphocytes were stimulated by DCs primed with the different P. gingivalis K-serotypes. T-lymphocytes stimulated by K1 or K2-primed DCs elicited higher levels of Th1 and Th17-associated cytokines, T-bet and RORC2 than T-lymphocytes stimulated with DCs primed with the other serotypes. Conversely, the serotypes K3-K5 induced higher levels of Th2-associated cytokines and GATA-3 than the others. Conclusions These results demonstrate that DCs primed with the different P. gingivalis K-serotypes elicited distinct T-cell responses. Strains K1 (W83) and K2 ( HG184) induced a Th1/Th17 pattern of immune response and K3 (A7A1-28), K4 ( ATCC®49417™), and K5 ( HG1690) a Th2 response. [ABSTRACT FROM AUTHOR]

Schistosome worms have been infecting humans for millennia, but it is only in the last half century that we have begun to understand the complexities of this inter-relationship. As our sophistication about the inner workings of every aspect of the immune system has increased, it has also become obvious that schistosome infections have broad ranging effects on nearly all of the innate and adaptive immune response mechanisms. Selective pressures on both the worms and their hosts, has no doubt led to co-evolution of protective mechanisms, particularly those that favor granuloma formation around schistosome eggs and immune suppression during chronic infection. The immune modulatory effects that chronic schistosome infection and egg deposition elicit have been intensely studied, not only because of their major implications to public health issues, but also due to the emerging evidence that schistosome infection may protect humans from severe allergies and autoimmunity. Mouse models of schistosome infection have been extremely valuable for studying immune modulation and regulation, and in the discovery of novel aspects of immunity. A progression of immune reactions occurs during granuloma formation ranging from innate inflammation, to activation of each branch of adaptive immune response, and culminating in systemic immune suppression and granuloma fibrosis. Although molecular factors from schistosome eggs have been identified as mediators of immune modulation and suppressive functions of T and B cells, much work is still needed to define the mechanisms of the immune alteration and determine whether therapies for asthma or autoimmunity could be developed from these pathways. [ABSTRACT FROM AUTHOR]

The development of collateral circulation is an inherent compensatory mechanism to restore impaired blood perfusion following artery stenosis and/or occlusion. This process, termed arteriogenesis, is driven by inflammation and involves a complex remodeling of pre-existing conduit vessels running in parallel to the occluded artery. Recent studies have unveiled roles for different immune cell subsets as regulators of arteriogenesis, including natural killer (NK) cells, T helper 17 (Th17) cells, regulatory T lymphocytes (Tregs), and functional subsets of macrophages (e.g., M2 macrophages). This review summarizes recent findings and discusses future research needed to better define the time during which each cellular subset is active and reveal further critical regulatory switches. [Copyright &y& Elsevier]

Abstract: Inflammatory mediators are responsible for the neuroinflammation observed in Alzheimer’s disease (AD), a phenomenon that might be the culprit of disease or, possibly, a reaction to pathology. To better investigate inflammation in AD we performed an extensive immunophenotypic and functional analysis of amyloid-beta (Aβ) stimulated T lymphocytes in patients with a diagnosis of AD comparing data to those obtained in individuals with mild cognitive impairment (MCI) or aged-matched healthy individuals (HC). Results showed that IL-21- and IL-9-producing Aβ stimulated CD4+ T cells, as well as IL-23- and IL-6-producing monocytes and CD4+ T cells expressing the RORγ and NFATc1 transcriptional factors (TF), were significantly increased, whereas IL-10-producing monocytes were decreased in AD. Notably, GATA-3 TF-expressing CD4+ T lymphocytes were significantly increased in MCI alone. Analysis of the post-thymic differentiation pathway indicated that Aβ specific naïve and central memory CD4+ T lymphocytes were diminished whereas effector memory and terminally differentiated CD4+ T lymphocytes were increased in AD and MCI compared to HC. Data herein indicate that cytokines (IL-21, IL-6, IL-23) and TF (RORγ) involved in the differentiation of Th-17 cells), as well as cytokines (IL-21, IL-22) generated by such cells, and IL-9, produced by Th-9 cells, are significantly increased in AD. This is accompanied by a shift of post-thymic differentiation pathways favoring the accumulation of differentiated, effector T lymphocytes. These data shed light on the nature of AD-associated neuroinflammation. A better understanding of the complexity of this phenomenon could facilitate the search for novel therapeutic strategies. [Copyright &y& Elsevier]

Abstract: In this work we evaluated the specific immune activation properties of different Bifidobacterium strains, some of the most relevant intestinal microorganisms. To this end, we examined the in vitro effect of 12 Bifidobacterium strains belonging to 4 different species, Bifidobacterium longum, Bifidobacterium breve, Bifidobacterium bifidum and Bifidobacterium animalis subsp. lactis, on the maturation pattern of human monocyte-derived dendritic cells (DCs), as well as in their ability to induce cytokine secretion. In addition, we determined peripheral blood mononuclear cell (PBMC) proliferation and cytokine expression after exposure to bacterial strains. All bifidobacteria tested were able to induce full DC maturation but showed differences in the levels of cytokine production, especially IL-12, IL-10, TNFα and IL-1β, suggesting that specific cytokine ratios could be used to predict the type of Th response that they may promote. In fact, analysis of cytokine production by PBMC showed that most of the tested B. animalis and B. longum strains induced the secretion of large amounts of IFNγ and TNFα, in agreement with the Th1 profile suggested by DC cytokine production. Remarkably, three of four B. bifidum strains induced poor secretion of these cytokines and significant amounts of IL-17, the main product of Th17 cells, in accordance with the high IL-1β/IL-12 ratio observed after DC stimulation. In conclusion, this work shows species and strain-specific immune effects of bifidobacteria and describes a valuable method for screening possible probiotic strains with different immunomodulatory properties. Notably, some B. bifidum strains seem to promote Th17 polarization, which could be useful for future probiotic applications. [Copyright &y& Elsevier]

Class II MHC molecules present processed peptides from exogenous antigens to CD4+helper T lymphocytes. In so doing, they are central to immunity, driving both the humoral and cell mediated arms of the immune response. Class II MHC molecules, and the genes encoding them, are expressed primarily in cells of the immune system (B cells, thymic epithelial cells, activated T cells and professional antigen presenting cells). The expression is also under developmental control. Research over the past 20 years have provided a clear understanding of the cis-elements and transcription factors that regulate the expression of Class II MHC genes Perhaps the most critical advance has been the discovery of CIITA, a non-DNA binding activator of transcription that is a master control gene for class II gene expression. Current research is focused on understanding the situations where class II MHC gene expression occurs in a CIITA-independent pathway, and the molecular basis for this expression. Finally, significant emphasis is being placed on targeting class II MHC transcription factors to either inhibit or stimulate the immune response to transplanted tissue or in cell based vaccines. This communication outlines recent advances in this field and discusses likely areas for future research. [ABSTRACT FROM AUTHOR]

Interleukin-4 (IL-4) mediates important pro-inflammatory functions in asthma including induction of the IgE isotype switch, expression of vascular cell adhesion molecule-1 (VCAM-1), promotion of eosinophil transmigration across endothelium, mucus secretion, and differentiation of T helper type 2 lymphocytes leading to cytokine release. Asthma is a complex genetic disorder that has been linked to polymorphisms in the IL-4 gene promoter and proteins involved in IL-4 signaling. Soluble recombinant IL-4 receptor lacks transmembrane and cytoplasmic activating domains and can therefore sequester IL-4 without mediating cellular activation. We report the results of initial clinical trials, which demonstrate clinical efficacy of this naturally occurring IL-4 antagonist as a therapeutic agent in asthma. [ABSTRACT FROM AUTHOR]

We studied mitogen- and antigen-induced interleukin 2 (IL-2) production in HTLV-Ill LAV infected and non-infected individuals and compared the results with T cell subpopulations. and with mitogen- and antigen-induced DNA synthesis and production of leucocyte migration inhibitory factor (LIF in order to understand the controversial findings related to IL-2 production in HTLV-III/V infection. The HTLV-llI/LAV antibody positive group showed immunologial defects: low T helper (Th) cells, high Th- suppressor (Th) cells, reduced mitogen- and antigen-induced DNA-synthesis. but LIE production comparable to the HTLV-lll/LAV antibody negative group. The total amount of IL-2, produced either as a response to a mitogenic stimulus or as a response to a soluble antigenic (purified protein derivative of tuberculin, PPD) stimulus, was lower in the HTLV-III/LAV antibody positive group. However, adjusting the IL-2 production to the amount of Th-cells showed that the IL-2 produced by a standard number of Th-cells after mitogen induction was similar in HTLV-lll/LAV infected and non-infected individuals. In contrast, the ability of Th-cells of infected persons to produce IL-I or to proliferate as a response to a soluble antigenic stimulus, was considerably diminished. We conclude that HTLV-lll infection leads to a selective incapability to mount a specific Th- cell response either due to an intrinsic defect in the Th-cell population or due to metabolic and/or functional disturbances in antigen-processing and presenting accessory cells. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a group of severe chronic inflammatory conditions of the human gastrointestinal tract. Murine models of colitis have been invaluable tools to improve the understanding of IBD development and pathogenesis. While the disease etiology of IBD is complex and multifactorial, CD4 + T helper cells have been shown to strongly contribute to the disease pathogenesis of IBD. Here, we present a detailed protocol of the preclinical model of T-cell transfer colitis, which can easily be utilized in the laboratory to study T helper cell functions in intestinal inflammation.

Background: Dipeptidyl peptidase-4 (DPP-4) rapidly inactivates incretin hormones and several chemokines, thus influencing chemokine function. There have recently been several reports that DPP-4 inhibitor therapy is associated with an increased risk of bullous pemphigoid (BP), an autoimmune skin disease. Previous studies have demonstrated an increase of CCL11/Eotaxin, a DPP-4 substrate, in serum and blister fluid from patients with BP. Serum levels of CCL22/macrophage-derived chemokine (MDC) and CXCL10/IP-10, other DPP-4 substrates, are also elevated in BP patients., Materials and Methods: In patients with type 2 diabetes, we investigated the effect of treatment with teneligliptin (a DPP-4 inhibitor) for 24 weeks on plasma levels of CCL11/Eotaxin, CCL22/MDC and CXCL10/IP-10 during a meal test. Ten consecutive patients with type 2 diabetes who showed inadequate glycemic control by metformin and/or sulfonylureas were recruited. A standard meal test was performed at baseline and after 24 weeks of treatment with teneligliptin at 20 mg/day. Blood samples were collected at 0, 30, 60 and 120 minutes after ingestion of the meal. In addition to plasma levels of the 3 chemokine, plasma DPP-4 enzyme activity and soluble DPP-4 antigen were measured., Results: Treatment with teneligliptin decreased hemoglobin A1c and reduced fasting plasma DPP-4 activity by 90.1% compared with baseline. Unexpectedly, plasma levels of all 3 chemokines (including CCL11/Eotaxin) were not increased after teneligliptin treatment, and instead were significantly lower at every point during the meal test., Conclusions: Teneligliptin reduced the plasma concentrations of 3 chemokines (DPP-4 substrates) that may be related to the occurrence of DPP4 inhibitor-associated BP (UMIN000012508)., (Copyright © 2020 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

An immunophenotyping analysis was performed in peripheral blood samples from seven patients with lung cancer unfit for surgery treated with stereotactic body radiotherapy (SBRT). The objective was to characterize the effect of SBRT on the host immune system. Four patients received 60 Gy (7.5 Gy × 8) and three 50 Gy (12.5 Gy × 4). Analyses were performed before SBRT, 72 h after SBRT, and at one, three, and six months after the end of SBRT. Of note, there was a specific increase of the immunoactive component of the immune system, with elevation of CD56+highCD16+ natural killer (NK) cells (0.95% at baseline to 1.38% at six months), and a decrease of the immunosuppressive component of the immune system, with decreases of CD4+CD25+Foxp3+CDA5RA− regulatory T cells (4.97% at baseline to 4.46% at six months), granulocytic myeloid-derived suppressor cells (G-MDSCs) (from 66.1% at baseline to 62.6% at six months) and monocytic (Mo-MDSCs) (8.2% at baseline to 6.2% at six months). These changes were already apparent at 72 h and persisted over six months. SBRT showed an effect on systemic immune cell populations, which is a relevant finding for supporting future combinations of SBRT with immunotherapy for treating lung cancer patients. [ABSTRACT FROM AUTHOR]

Background: The imbalance of Th17/Treg cells and the IL-23/IL-17 axis have been confirmed to be associated with sepsis and various inflammatory diseases. Early enteral nutrition (EEN) can modulate the inflammatory response, improve immune dysfunction, and prevent enterogenic infection in critically ill patients; however, the precise mechanisms remain unclear. Considering the important roles of Th17 and Treg lymphocytes in the development of inflammatory and infectious diseases, we hypothesized that EEN could improve the immune dysfunction in sepsis by maintaining a balanced Th17/Treg cell ratio and by regulating the IL-23/IL-17 axis., Aim: To investigate the effects of EEN on the Th17/Treg cell ratios and the IL-23/IL-17 axis in septic patients., Methods: In this prospective clinical trial, patients were randomly divided into an EEN or delayed enteral nutrition (DEN) group. Enteral feeding was started within 48 h in the EEN group, whereas enteral feeding was started on the 4th day in the DEN group. The Th17 and Treg cell percentages and the interleukin levels were tested on days 1, 3, and 7 after admission. The clinical severity and outcome variables were also recorded., Results: Fifty-three patients were enrolled in this trial from October 2017 to June 2018. The Th17 cell percentages, Th17/Treg cell ratios, IL-17, IL-23, and IL-6 levels of the EEN group were lower than those of the DEN group on the 7th day after admission ( P < 0.05). The duration of mechanical ventilation and of the intensive care unit stay of the EEN group were shorter than those of the DEN group ( P < 0.05). However, no difference in the 28-d mortality was found between the two groups ( P = 0.728)., Conclusion: EEN could regulate the imbalance of Th17/Treg cell ratios and suppress the IL-23/IL-17 axis during sepsis. Moreover, EEN could reduce the clinical severity of sepsis but did not reduce the 28-d mortality of septic patients., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest.

Purpose: The evaluation of regulatory T (Treg) (CD4 + CD25 high CD127 neg ) lymphocyte count with respect to the T helper (TH) (CD4) number has been shown to represent the main immune parameters capable of signifying the functional status of the anticancer immunity in cancer patients. This study is aimed to explore a correlation between therapy efficacy and changes in Treg/TH ratio and other biochemical and haematological parameters in patients with metastatic colorectal cancer (mCRC)., Experimental Design: Measurements of regulatory T cells were performed by flow cytometric analysis pre- and post-therapies in a prospective study., Results: We investigated levels of Treg/TH ratio in the peripheral blood of 25 mCRC patients pre- and post-chemotherapy ± targeted therapy. There were significant differences in levels of Treg/TH ratio pre- and post-treatments among patients on study, patients with partial response (PR), stable disease (SD) and progressive disease (PD) ( P = 0.012, P = 0.011, and P = 0.043, respectively). Moreover, the relative change in Treg/TH ratio showed statistically significant difference among patients with PD as compared to those with PR and SD. Our findings demonstrated a statistically significant strong correlation between the relative change in Treg/TH ratio and therapeutic response. (Spearman's rho= 0.788/ p <0.001)., Conclusions: The monitoring of the relative change in Treg/TH ratio could constitute a promising clinical index for response prediction and a timely change in regimen. Further prospective evaluations of these parameters investigated, particularly their association with overall survival, are warranted., Competing Interests: CONFLICTS OF INTEREST The authors declare there is no potential conflicts of interests.

Objective: The biological mechanisms linking obesity to insulin resistance have not been fully elucidated. We have shown that insulin resistance or glucose intolerance in diet-induced obese mice is related to a shift in the ratio of pro- and anti-inflammatory T cells in adipose tissue. We sought to test the hypothesis that the balance of T-cell phenotypes would be similarly related to insulin resistance in human obesity., Approach and Results: Healthy overweight or obese human subjects underwent adipose-tissue biopsies and quantification of insulin-mediated glucose disposal by the modified insulin suppression test. T-cell subsets were quantified by flow cytometry in visceral (VAT) and subcutaneous adipose tissue (SAT). Results showed that CD4 and CD8 T cells infiltrate both depots, with proinflammatory T-helper (Th)-1, Th17, and CD8 T cells, significantly more frequent in VAT as compared with SAT. T-cell profiles in SAT and VAT correlated significantly with one another and with peripheral blood. Th1 frequency in SAT and VAT correlated directly, whereas Th2 frequency in VAT correlated inversely, with plasma high-sensitivity C-reactive protein concentrations. Th2 in both depots and peripheral blood was inversely associated with systemic insulin resistance. Furthermore, Th1 in SAT correlated with plasma interleukin-6. Relative expression of associated cytokines, measured by real-time polymerase chain reaction, reflected flow cytometry results. Most notably, adipose tissue expression of anti-inflammatory interleukin-10 was inversely associated with insulin resistance., Conclusions: CD4 and CD8 T cells populate human adipose tissue and the relative frequency of Th1 and Th2 are highly associated with systemic inflammation and insulin resistance. These findings point to the adaptive immune system as a potential mediator between obesity and insulin resistance or inflammation. Identification of antigenic stimuli in adipose tissue may yield novel targets for treatment of obesity-associated metabolic disease., (© 2014 American Heart Association, Inc.)

Background: Th17 lymphocytes have important roles in inflammation and autoimmune disease. Research on relationship between Th17 lymphocytes and pain associated with lumbar disc herniation (LDH) is limited. The purpose of this study was to examine the association of pain and Th17 lymphocyte and interleukin (IL)-17 levels in patients with herniated and non-herniated lumbar discs., Methods: Thirty-four patients with single lumbar intervertebral disc herniation (median age, 44 years), and 17 healthy adults (median age, 37 years) were enrolled. Patients were divided into 2 groups depending on their magnetic resonance imaging (MRI) results and visual observations during surgery (group P, non-ruptured disc, n=15; group E, ruptured disc, n=19). Patients received posterior or transforaminal lumbar interbody fusion. Preoperative pain intensity was recorded using a visual analogue scale (VAS) score. The percentage of Th17 lymphocytes and IL-17 and prostaglandin E2 (PGE2) levels in peripheral blood were determined. Disc tissue was examined by immunohistochemistry for Th17 and IL-17 expression., Results: Preoperative VAS pain scores were significantly higher in group E than group P (8.32±1.04 vs. 6.33±2.68, respectively, p=0.009). Similarly, PGE2 level was greater in group E than group P (3.75±1.41pg/ml vs. 2.63±0.89pg/ml, respectively, p=0.011). Compared to healthy controls (1.05±0.19%), the percentage of Th17 cells was significantly greater in group P (1.52±0.62%, p=0.031), and the percentage in group E (2.99±1.09%, p<0.001) was significantly greater than in group P. The IL-17 expressions were similar. VAS pain score was positively correlated with Th17 proportion (r=0.489, p=0.003), and IL-17 concentration (r=0.458, p=0.007). PGE2 was also positively correlated with Th17 proportion (r=0.539, p=0.001), and IL-17 concentration (r=0.500, p=0.003). The expression of IL-17 was higher in the cells of group E and group P compared with normal tissue (p<0.001)., Conclusions: Immune system activation is responsible, at least in part, for the pain experienced by patients with LDH, and increased levels of Th17 lymphocytes and IL-17 contribute to the pain., (Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.)