Influence Of CD4 Research Articles

P-280 Influences of CD8(+) tissue resident memory T cells on eutopic endometrial immune microenvironment and endometrial receptivity of minimal/mild endometriosis

Abstract Study question Our study aimed to focused on the influence of CD8+ tissue resident memory T cells (CD8+ TRM) on endometrial immune microenvironment and endometrial receptivity. Summary answer CD8+TRM participated in inflammatory endometrial immune microenvironment, influenced expression of endometrial receptivity and decidualization markers of stromal cells of eutopic endometrium of minimal/mild endometriosis. What is known already CD8+ tissue resident memory T cells (CD8+ TRM) are abundant in endometrium,CD8+ TRM have important physiological functions and of pathological significance in endometrium. Study design, size, duration Endometrial samples were collected using Pipelle sampling from women with or without endometriosis (minimal/mild) during hysteroscopy-laparoscopy. Tissue for immunofluorescence was fixed in 4% paraformaldehyde, for cell analysis was isolated into single cell immediately. Participants/materials, setting, methods We analyzed number variation, tissue location, cytotoxicity, degranulation and cytokine secretion of CD8+TRM in endometriosis and control during menstrual cycle through flow cytometry and polychromatic tissue immunofluorescence. We cocultured CD8+TRM and endometrial stromal cell to know the influence of CD8+TRM to endometrial receptivity and decidualization. The concentration of TNF-α, IFN-γ, IGFBP-1 and PRL were analyzed via ELISA and q-PCR. Western blot and q-PCR were used to test the expression level of HOXA10 and FOXO1. Main results and the role of chance Flow cytometry founded that the number of CD8+TRM in proliferative phase were more than secretory phase in both endometriosis and control. CD8+TRM were not only scattered in stroma of endometria, and also gathered in lymphoid aggregates. During secretory phase, the cytotoxicity, degranulation, and inflammatory cytokine expression resourced from CD8+ TRM were higher in endometriosis than control. CD8+TRM inhibited the expression of endometrial receptivity markers (HOXA10 and FOXO1) and decidualization markers (IGFBP-1 and PRL) of endometrial stromal cells in coculture system. When blocking the IFN-γ in coculture system, the expression of endometrial receptivity markers and decidualization markers were improved. Limitations, reasons for caution The mechanism of CD8+TRM influence on endometrial receptivity and decidualization of endometriosis is needed to further investigation. Wider implications of the findings CD8+TRM participated in inflammatory endometrial immune microenvironment, influenced expression of endometrial receptivity and decidualization markers of stromal cells of eutopic endometrium of minimal/mild endometriosis. CD8+TRM and its secretion of IFN-γ could be immunotherapeutic target for defective endometrial receptivity of endometriosis. Trial registration number NA

Potential role of Vitamin D in immune response in patients with viral hepatitis

To study the relationship of Vitamin D with innate and adaptive immune response parameters in chronic hepatitis B and C patients. The laboratory data between January 1, 2013 and February 1, 2023, for patients with chronic hepatitis B (CHB), and chronic hepatitis C (CHC) were extracted. Serum 25-hydroxyl vitamin D, hepatitis B virus serological markers, complements, and subsets of T lymphocytes were determined. Study cohorts were divided into groups based on serum 25-hydroxyl vitamin D levels with further evaluation of laboratory data. In CHB and CHC patients the percentage of CD4+ T lymphocytes and the CD4+/CD8+ ratio significantly decreased (P < 0.05), but the percentage of CD8+ increased (P < 0.05) compared to the control group. In CHB patients Vitamin D decrease was significant (P < 0.001) but not in CHC patients. Vitamin D showed a moderate negative influence on the CD8 cell count in CHB patients. The positive ratio of HBV DNA and HBsAg decreased with increasing serum vitamin D levels. The vitamin D deficient group showed significantly lower antibody production compared to the normal group, and exhibited significantly decreased CD4 numbers and increased CD8 numbers (P < 0.05 and P < 0.001, respectively), while the CD4/CD8 ratio was also significantly decreased in the insufficiency group (P < 0.001). Complement C3 levels were not associated with CD4 and CD8, but had an inverse relation with Vitamin D. Vitamin D levels were significantly associated with complement C3, CD8+, CD4+, CD19+ cells, and HBV DNA levels. Vitamin D may be a modulator of immune function not only via CD8+ and CD4+ cells but also via CD19+ cells in the course of chronic HBV infection. The negative relationship between vitamin D and complement C3 needs elucidation. Moreover, the increased proportion of B cells and decreased CD4+ cells in Vitamin D deficiency disrupt the immune response against HBV since the expected antibody response was not obtained despite the increase in B cell ratio. This indicates an influence of CD4+ cells for B cell functionality. In summary, sufficient levels of Vitamin D may lead to a sustained virological response that is debatable by artificially correcting the deficiency.

The Influence of CD4+ T-Lymphocytes on the Strength of Anti-Diphtheria Immunity in Adult People Living with HIV

The Influence of CD4+ T-Lymphocytes on the Strength of Anti-Diphtheria Immunity in Adult People Living with HIV

Changes in intestinal microbiota in HIV-1-infected subjects following cART initiation: influence of CD4+ T cell count

The roles of immunodeficiency and combined antiretroviral therapy (cART) in shaping the gut microbiota in HIV-1-infected subjects (HISs) have not been described thoroughly by time-series investigations. In this study, 36 antiretroviral-naïve HISs were enrolled to prospectively assess alterations in the fecal microbiota and plasma markers of microbial translocation and inflammation with cART. At baseline, the species α-diversity of the fecal microbiota was significantly lower in HISs with a CD4+ T cell count <300/mm3 than in HISs with a CD4+ T cell count >300/mm3 (Shannon index: Median 2.557 vs. 2.981, P = 0.006; Simpson index: Median 0.168 vs. 0.096, P = 0.004). Additionally, the baseline α-diversity indices correlated with CD4+ T cell counts (Shannon index: r = 0.474, P = 0.004; Simpson index: r = −0.467, P = 0.004) and the specific plasma biomarkers for microbial translocation and inflammation. After cART introduction, the species α-diversity of fecal microbiota in HISs with CD4+ T cell counts <300/mm3 was significantly restored (Shannon index: Median 2.557 vs. 2.791, P = 0.007; Simpson index: Median 0.168 vs. 0.112, P = 0.004), while the variances were insignificant among HISs with CD4+ T cell counts >300/mm3 (Shannon index: Median 2.981 vs. 2.934, P = 0.179; Simpson index: Median 0.096 vs. 0.119, P = 0.082). Meanwhile, with cART introduction, alterations in the gut microbial composition were more significant in the subgroup with CD4+ T cell counts >300/mm3, corresponding to increases in the specific plasma inflammatory markers. These findings implicated the interactive roles of immunodeficiency and cART for affecting gut microbiota in HIV-1-infected individuals, providing new insights into intestinal microbiome dysbiosis related to HIV-1 infection.

Percentage and function of CD4+CD25+ regulatory T cells in patients with hyperthyroidism.

The current study observed the percentage of peripheral blood (PB) CD4+CD25+ regulatory T cells (Tregs) and the influence of CD4+CD25+ Tregs on the proliferation of naïve CD4 T cells in patients with hyperthyroidism. Furthermore, preliminary discussions are presented on the action mechanism of CD4+CD25+ Tregs on hyperthyroidism attacks. The present study identified that compared with the percentage of PB CD4+CD25+ Tregs in healthy control subjects, no significant changes were observed in the percentage of PB CD4+CD25+ Tregs in patients with hyperthyroidism (P>0.05). For patients with hyperthyroidism, CD4+CD25+ Tregs exhibited significantly reduced inhibition of the proliferation of naïve CD4 T cells and decreased secretion capacity on the cytokines of CD4 T cells, compared with those of healthy control subjects (P<0.05). In addition, it was demonstrated that thyroid function of patients with hyperthyroidism was significantly improved (P<0.05) subsequent to receiving medication. Compared with the percentage of PB CD4+CD25+ Tregs in patients with hyperthyroidism before treatment, no significant changes were observed in the percentage of PB CD4+CD25+ Tregs in hyperthyroidism patients following treatment (P>0.05). In the patients with hyperthyroidism, following treatment, CD4+CD25+ Tregs exhibited significantly increased inhibition of the proliferation of naïve CD4 T cells and increased secretion capacity of CD4 T cell cytokines, compared with those of the patients with hyperthyroidism prior to treatment (P<0.05). PB CD4+CD25+ Tregs function was decreased in patients with hyperthyroidism, and its non-proportional decrease may be closely associated with the occurrence and progression of hyperthyroidism.

Loss of amplitude of accommodation in pre-presbyopic HIV and AIDS patients under treatment with antiretrovirals

Background: The prevalence of HIV and AIDS is causing an enormous public health burden. Its manifestations spare no organ. Ocular complications are mainly attributed to various opportunistic infections which are directly or indirectly caused by immune deficiency.Purpose and aim: The purpose of this study was to determine the effect of HIV and AIDS on subjective amplitude of accommodation of patients under treatment with antiretrovirals and then to compare their results to those of control subjects.Methods: The study took place over a period of 10 months. A quantitative study was carried out on 58 subjects (29 ± 5.5 years) with HIV and AIDS and 35 (28.67 ± 4.6 years) controls of similar age. Amplitude of accommodation was measured using the subjective Royal Air Force push-up method. The influence of CD4+ cell count was also recorded.Results: People with HIV and AIDS had lower mean amplitude of accommodation (5.69 ± 0.88 D) compared to controls (8.53 ± 1.2 D). The decrease in amplitude of accommodation did not show any correlation with the CD4+ cell count. Lower amplitude of accommodation exists in people living with HIV and AIDS when compared with age-related healthy people.Conclusion: The results suggest that patients with HIV and AIDS on antiretroviral drugs (ARVs) have reduced amplitude of accommodation and might experience presbyopia earlier in life than participants without HIV and AIDS. The reduced amplitude of accommodation could be the initial presentation of HIV infection before the systemic manifestation. The possible causes could be the direct neuronal infection by HIV-1, ARVs use, pathological changes of the lens and ciliary muscle or the sensory component of the visual system. It is unknown whether the reduced amplitude of accommodation occurred prior to antiretroviral therapy or represents an ongoing injury to the eye and visual system by the HIV.

The Influence of CD8(+) T Lymphocytes and NK Cells in Cases of Squamous Cell Carcinoma and Their Relationship With the Progression of the Lesion

To evaluate the presence of CD8 T lymphocytes and natural killer (NK) cells through immunoexpression of CD57 and CD8 in metastatic and non-metastatic lower lip squamous cell carcinoma (LLSCC).

Periportal fibrosis, liver and spleen sizes among S. mansoni mono or co-infected individuals with human immunodeficiency virus-1 in fishing villages along Lake Victoria shores, North-Western, Tanzania.

BackgroundThe pathogenesis of S. mansoni infection involves chronic inflammatory responses to parasite eggs which can be associated with a characteristic periportal fibrosis (PPF) and the progression to severe hepatosplenic disease. The effects of HIV-1 co-infection and the influence of CD4+ cell numbers on these clinical manifestations of chronic S. mansoni are not known. To understand the effects of HIV-1 co-infection on these morbidities, we examined S. mansoni ultrasound-detectable morbidities in relation to HIV-1 infection and CD4+ cell counts, and other factors in fishing communities where the two infections are present.MethodsUltrasonographical examination was conducted during a cross-sectional study of 1,671 (aged 21–55 years) individuals in North-Western Tanzania. Blood samples were obtained for HIV-1 screening and CD4+ cell quantification. A single stool sample was examined for S. mansoni eggs using the Kato-Katz technique. A questionnaire was used to collect socio-demographic-economic information.ResultsThe prevalence of PPF (grade C-F) was 13.79% and 15.01% for the HIV-1 infected and non-infected individuals (P = 0.72). Male gender (P< 0.001), age group 21–30 years (P< 0.028) and, residential time of 11–20 (P< 0.01) and ≥21 years (P< 0.01) were associated with PPF in S. mansoni infected individuals. The height-adjusted measurements of the left liver lobe were significantly larger in HIV-1/S. mansoni co-infected compared to S. mansoni only-infected individuals (t = −2.0702, P< 0.039). Predictors of the height-adjusted measurements of the left liver lobe and spleen were age, male gender, malaria infection, fishing occupation, village of residence and heavy intensity of S. mansoni infection. After accounting for these factors, neither HIV-1 infection nor CD4+ cell counts predicted PPF, hepatosplenomegaly, measurements of the liver or spleen. Height-adjusted ultrasound measurements of the left liver lobe did not correlate with the CD4+ cells counts in co-infected individuals (r = −0.16, P = 0.084).ConclusionS. mansoni-related PPF, liver and spleen enlargement are prevalent in the study population. The intensity of S. mansoni infection was associated with the enlargement of liver, spleen and hepatosplenomegaly. The PPF grades observed were similar in both HIV-1/S. mansoni co-infected and in those only infected with S. mansoni. There was no evidence that HIV-1 infection or CD4+ cells counts were associated with these S. mansoni morbidities.

T-bet modulates the antibody response and immune protection during murine malaria.

CD4(+) T-cell subtypes govern the synthesis of different Ab isotypes and other immune functions. The influence of CD4(+) T-cell differentiation programs on isotype switching and other aspects of host immunological networks during malaria infection are currently poorly understood. Here, we used Tbx21(-/-) mice deficient for T-bet, a regulator of Th1 CD4(+) T-cell differentiation, to examine the effect of Th1 CD4(+) T cells on the immune protection to nonlethal murine malaria Plasmodium yoelii 17XNL. We found that Tbx21(-/-) mice exhibited significantly lower parasite burden that correlated with elevated levels of IgG1, indicating that T-bet-dependent Ab isotype switching may be responsible for lower parasite burden. Absence of T-bet was also associated with a transient but significant loss of T cells during the infection, suggesting that T-bet may suppress malaria-induced apoptosis or induce proliferation of T cells. However, Tbx21(-/-) mice produced greater numbers of Foxp3(+) CD25(+) regulatory CD4(+) T cells, which may contribute to the early contraction of T cells. Lastly, Tbx21(-/-) mice exhibited unimpaired production of IFN-γ by a diverse repertoire of immune cell subsets and a selective expansion of IFN-γ-producing T cells. These observations may have implications in malaria vaccine design.

Influence of CD8 T cell priming in liver and gut on the enterohepatic circulation

The enterohepatic circuit of T cells may be responsible for the development of autoimmune liver disease. We employed transgenic mice to characterize phenotype and migration patterns of CD8 T cells activated in liver and gut. We studied the migration of antigen-specific CD8 T cells primed in liver or gut after transfer in wild-type mice or mice that express ovalbumin in liver or gut. We performed transcriptome analysis of these two distinct T cell populations and confirmed our findings by flow cytometry. Specific migration patterns were induced by activation of CD8 T cells in gut or liver. Gut-activated CD8 T cells expressed α4β7 and CCR9 and migrated to the gut and to the liver. Liver-activated T cells expressed integrins α4, α6, β1, α4β7 as well as CD62L, Ly6C, and neuropilin-1 and retained the capability to re-circulate through lymph nodes. Presence of the antigen increased retention of both types of activated T cells in the liver, but migration of liver-activated T cells to the gut was prohibited. CD8 T cells primed in the liver in vivo are not capable of migrating to the gut, implying that the enterohepatic circuit of CD8 T cells is in fact a one-way road from the gut to the liver. Priming of CD8 T cells in the liver results in a distinct phenotype with attributes of central memory cells and induces a unique homing pattern. Gut-primed T cells preferentially home to the liver, in principle enabling them to induce autoimmune liver disease.

PD-1(+) immune cell infiltration inversely correlates with survival of operable breast cancer patients.

The programmed death-1 (PD-1) molecule is mainly expressed on functionally "exhausted" CD8(+) T cells, dampening the host antitumor immune response. We evaluated the ratio between effective and regulatory T cells (Tregs) and PD-1 expression as a prognostic factor for operable breast cancer patients. A series of 218 newly diagnosed invasive breast cancer patients who had undergone primary surgery at Ruijin Hospital were identified. The influence of CD8(+) cytotoxic T lymphocytes, FOXP3(+) (Treg cell marker), and PD-1(+) immune cell counts on prognosis was analyzed utilizing immunohistochemistry. Both PD-1(+) immune cells and FOXP3(+) Tregs counts were significantly associated with unfavorable prognostic factors. In bivariate, but not multivariate analysis, high tumor infiltrating PD-1(+) cell counts correlated with significantly shorter patient survival. Our results suggest a prognostic value of the PD-1(+) immune cell population in such breast cancer patients. Targeting the PD-1 pathway may be a feasible approach to treating patients with breast cancer.

Risk Factors for Anal Cancer in Persons Infected With HIV: A Nested Case-Control Study in the Swiss HIV Cohort Study

Although persons infected with human immunodeficiency virus (HIV), particularly men who have sex with men, are at excess risk for anal cancer, it has been difficult to disentangle the influences of anal exposure to human papillomavirus (HPV) infection, immunodeficiency, and combined antiretroviral therapy. A case-control study that included 59 anal cancer cases and 295 individually matched controls was nested in the Swiss HIV Cohort Study (1988-2011). In a subset of 41 cases and 114 controls, HPV antibodies were tested. A majority of anal cancer cases (73%) were men who have sex with men. Current smoking was significantly associated with anal cancer (odds ratio (OR) = 2.59, 95% confidence interval (CI): 1.25, 5.34), as were antibodies against L1 (OR = 4.52, 95% CI: 2.00, 10.20) and E6 (OR = ∞, 95% CI: 4.64, ∞) of HPV16, as well as low CD4+ cell counts, whether measured at nadir (OR per 100-cell/μL decrease = 1.53, 95% CI: 1.18, 2.00) or at cancer diagnosis (OR per 100-cell/μL decrease = 1.24, 95% CI: 1.08, 1.42). However, the influence of CD4+ cell counts appeared to be strongest 6-7 years prior to anal cancer diagnosis (OR for <200 vs. ≥500 cells/μL = 14.0, 95% CI: 3.85, 50.9). Smoking cessation and avoidance of even moderate levels of immunosuppression appear to be important in reducing long-term anal cancer risks.

How Numbers, Nature, and Immune Status of Foxp3+ Regulatory T-Cells Shape the Early Immunological Events in Tumor Development

The influence of CD4+CD25+Foxp3+ regulatory T-cells (Tregs) on cancer progression has been demonstrated in a large number of preclinical models and confirmed in several types of malignancies. Neoplastic processes trigger an increase of Treg numbers in draining lymph nodes, spleen, blood, and tumors, leading to the suppression of anti-tumor responses. Treg-depletion before or early in tumor development may lead to complete tumor eradication and extends survival of mice and humans. However this strategy is ineffective in established tumors, highlighting the critical role of the early Treg-tumor encounters. In this review, after discussing old and new concepts of immunological tumor tolerance, we focus on the nature (thymus-derived vs. peripherally derived) and status (naïve or activated/memory) of the regulatory T-cells at tumor emergence. The recent discoveries in this field suggest that the activation status of Tregs and effector T-cells (Teffs) at the first encounter with the tumor are essential to shape the fate and speed of the immune response across a variety of tumor models. The relative timing of activation/recruitment of anti-tumor cells vs. tolerogenic cells at tumor emergence appears to be crucial in the identification of tumor cells as friend or foe, which has broad implications for the design of cancer immunotherapies.

Influence of CD8+ T regulatory cells on intraocular tumor development

The interior of the eye, or uvea, is a site of immune privilege where certain immune responses are attenuated or completely excluded to protect non-regenerating tissues essential for vision. One consequence of this immunoregulation is compromised immune mediated elimination of intraocular tumors. For example, certain murine tumor cell lines which are rejected by host immune responses when transplanted in the skin grow progressively when placed in the anterior chamber (a.c.) of the eye. Progressive ocular tumor growth occurs despite induction of tumor-specific CD8+ T cell responses capable of eliminating a subsequent tumor challenge in the skin or opposite eye. Why these CD8+ T effectors fail to eliminate established ocular tumors is not known. It is well appreciated that growth of tumors in the a.c. induces the generation of immunosuppressive CD8+ T regulatory (Treg) cells. However, the contribution of CD8+ Treg in ocular tumor progression remains unclear. Several studies indicate that these CD8+ Treg target responding CD4+ T cells to inhibit their induction of macrophage-dependent delayed type hypersensitivity (DTH) responses to tumor antigens (Ags). However, induction of tumor-specific CD4+ T cell responses does not assure intraocular tumor elimination. This review is focused on how CD8+ Treg could influence the tumoricidal activity of ocular tumor-specific CD8+ T effector cells.

In vivo injection of CD4+CD25+ regulatory T cells affects renal impairment in MRL/lpsjmice

Objective To investigate the influence of CD4+CD25+ regulatory T cells (Tregs) on the disease progression in MRL/lps mice. Methods Tregs were separated by using magnetic beads from splenic cells of MRL/lps mice and BALB/c mice, and concentrated. Twenty-four MRLAps mice were equally divided into 3 groups, test group 1 injected with Tregs from MRL/lps mice, test group 2 injected with Tregs from BALB/c mice, and control group injected with physiological sodium chloride solution. Three weeks later, the levels of urine protein as well as serum anti-dsDNA antibody were determined; subsequently, the mice were sacrificed followed by histopathological and immunopathological examination of renal tissue. Results A significant decline was observed in the test group 1 compared with the test group 2 and control group in the urine protein score (10.63 ± 4.17 vs. 20.00 ± 5.35 and 18.75 ± 8.34, both P 0.05). There was no statistical difference between the test group 2 and control group in terms of any of the above parameters (all P > 0.05). Conclusions Injection of Tregs from homologous mice could significantly down-regulate proteinuria degree, serum anti-dsDNA antibody level, glomerular sclerosis index and IgG immune complex level in renal tissue, and thereby decelerate the progression of renal impairment in MRL/lps mice. Key words: T-lymphocytes, regulatory; Kidney; Mice, linbred MRL lps; Antibodies, antinuclear

Cancer Risk in HIV-Infected Persons: Influence of CD4 + Count

Persons infected with HIV are at increased risk for all cancers known or suspected to have an infectious cause, an effect believed to be primarily mediated by lowered host immunity via the depletion of CD4(+) cells. Whereas Kaposi sarcoma and non-Hodgkin lymphoma were recognised as AIDS-defining illnesses early in the HIV epidemic, the influence of declining CD4(+) count on other infection-related cancers has taken longer to establish, undoubtedly because the association is weaker and the dose-response relationship is less steep. However, following improved survival made possible by combined antiretroviral therapy, declining CD4(+) count starts showing an impact on the natural history of various carcinogenic infections and on the risk for an increasingly wide range of cancers, including Hodgkin lymphoma, cervical, anal and liver cancers.

The influence of CD4 T‐cell subsets on control of CD4 T‐cell‐mediated graft‐versus‐host disease

In this study, we tested the effect of different T-cell subpopulations on antigen driven effector cell expansion in lymphopenic hosts, making use of an experimental model of graft-versus-host disease (GVHD). Fluorescence-activated cell sorted (FACS) naïve CD4 T cells from C57BL/6 mice, transferred into lymphopenic F1 (C57BL/6 x BALB/c) Rag-deficient hosts, proliferated extensively and migrated systemically causing acute GVHD within 4 weeks after transfer. Adoptive hosts of CD4 memory T cells on the other hand developed milder symptoms of GVHD with later onset. T-cell expansion and migration to peripheral sites as well as development of GVHD were prevented when naïve T cells were transferred together with CD4(+) CD25(+) T cells, but co-transfer of memory T cells with naïve T cells could not prevent GVHD, although its onset was delayed. OX40, a costimulatory marker that is upregulated at an early time point after T-cell activation and enhances T-cell proliferation, cytokine secretion and survival, was strongly upregulated during GVH responses. Naïve T cells deficient in OX40 expression caused markedly reduced GVH in onset and severity despite some level of expansion in the adoptive host, suggesting an important role of this molecule in the immune pathology of GVHD.

The influence of CD4 + CD25 + Foxp3 + regulatory T cells on the immune response to rotavirus infection

Rotavirus (RV) infection of the intestine is the major cause of severe dehydrating diarrhea in infants around the world. Although protective immunity against RV, especially acquired B and T-cell responses, has been extensively studied, our understanding of RV immunity remains incomplete. In addition, the interaction between various protective immune mechanisms in the gut and specific enteric immune suppressor systems that normally exert a regulatory function on mucosal immunity has not been extensively investigated. Among the candidate suppressor systems, we hypothesized that CD4 + CD25 + Foxp3 + regulatory T (Treg) cells may play a role in modulating RV immunity since such cells are naturally present in large numbers in the intestine and function nonspecifically. Here we demonstrate that neonatal murine RV (EC) infection induces an expansion of the Treg cell population and the magnitude of the T cell mediated immune response is modulated by Treg cells. Accordingly, when natural Treg cells in neonatal mice were depleted before virus infection, both CD4 + and CD8 + T-cell responses to RV, such as proliferation and IFN-γ secretion, were enhanced in mesenteric lymph nodes (MLNs) and the spleen. Interestingly, increased proliferation of CD19 + B cells from Treg cell depleted animals was also observed. Finally, we analyzed the in vivo effect of the Treg cell depletion on diarrheal disease, virus shedding and IgA RV-specific response. Treg cell depletion did not affect these functions. Our studies of immune modulatory Treg cells in the RV infection model may promote a better understanding of the basis for RV immunity as well as providing valuable clues for the development of more immunogenic RV vaccines.

Influence of CD4+/CD25+ regulatory T cells on atherogenesis in patients with end-stage kidney disease

Atherosclerosis, which is influenced by both traditional and nontraditional cardiovascular risk factors and has been characterized as an inflammatory process, is considered to be the main cause of the elevated cardiovascular risk associated with chronic kidney disease. The inflammatory component of atherosclerosis can be separated into an innate immune response involving monocytes and macrophages that respond to the excessive uptake of lipoproteins and an adaptive immune response that involves antigen-specific T cells. Concurrent with the influx of immune cells to the site of atherosclerotic lesion, the role of the adaptive immune response gradually increases. One of those cells are represented by the CD4+/CD25+ Tregs, which play indispensable roles in the maintenance of natural self-tolerance and negative control of pathological, as well as physiological, immune responses. Altered self-antigens such as oxidized LDLs may induce the development of CD4+/CD25+ Tregs with atheroprotective properties. However, atherosclerosis may be promoted by an imbalance between regulatory and pathogenic immunity that may be represented by the low expression of the forkhead box transcription factor (Foxp3) in CD4+/CD25+ Tregs. Such a defect may break immunologic tolerance and alter both specific and bystander immune suppression, leading to exacerbation of plaque development. Patients with end-stage kidney disease (ESKD) display a cellular immune dysfunction and accelerated atherosclerosis. Uremic solutes that accumulate during ESKD may be involved in these processes. In patients with ESKD and especially in those that are chronically hemodialyzed, oxidative stress induced by oxidized LDLs may increase CD4+/CD25+ Treg sensitivity to Fas-mediated apoptosis as a consequence of specific dysregulation of IL-2 expression. This review will focus on the current state of knowledge regarding the influence of CD4+/CD25+ Tregs on atherogenesis in patients with ESKD, and the potential effect of statins on the circulating number and the functional properties of these cells.

Influence of CD4 T cell help and Tregs in diabetes induction in RIP‐GP mice

Recently, we have developed a virus‐free protocol, which induces Type 1 Diabetes (T1D) in two different RIP‐GP strains with different disease kinetics and incidence. RIP‐GP Arm and RIP‐GP Berlin mice express the glycoprotein (GP) from the lymphocytic choriomeningitis virus (LCMV) strains Armstrong and WE, respectively, under control of the rat insulin promoter resulting in pancreatic LCMV‐GP expression. Our diabetes induction protocol induced T1D in all RIP‐GP Berlin mice seven to twelve days after treatment. In contrast, only maximally 35% of RIP‐GP Arm mice developed transient T1D from day nine onwards. We then analyzed whether LCMV‐specific Smarta CD4 T helper cells would increase diabetes incidence in RIP‐GP Arm mice and whether Smarta CD4 regulatory T cells (Tregs) would decrease T1D incidence in RIP‐GP Berlin mice. Transfer of Smarta T helper cells indeed increased T1D kinetics and incidence in RIP‐GP Arm mice whereas transfer of Smarta Tregs reduced T1D incidence in RIP‐GP Berlin mice to below 30%. In the future, we will analyze the mechanisms of how LCMV‐specific CD4 T helper and Treg cells influence T1D development in the two RIP‐GP strains.