scholarly journals The Effect of Age on the Immunogenicity of the Live Attenuated Zoster Vaccine Is Predicted by Baseline Regulatory T Cells and Varicella-Zoster Virus-Specific T Cell Immunity

2019 ◽  
Vol 93 (15) ◽  
Author(s):  
Adriana Weinberg ◽  
Lei Pang ◽  
Michael J. Johnson ◽  
Yupanqui Caldas ◽  
Alice Cho ◽  
...  
Keyword(s):  
Older Adults ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Varicella Zoster Virus ◽  
Regulatory T Cell ◽  
Zoster Vaccine ◽  
Varicella Zoster ◽  
Effect Of Age

ABSTRACT Older age is associated with increased infectious morbidity and decreased immune responses to vaccines, but the mechanisms that mediate this effect are incompletely understood. The efficacy and immunogenicity of the live attenuated zoster vaccine (ZVL) have a very-well-described negative association with the age of the vaccinee. In a study of 600 ZVL recipients 50 to >80 years of age, we investigated immunological factors that might explain the effect of age on the immunogenicity of ZVL. Using FluoroSpot assays and flow cytometry, we determined that varicella-zoster virus (VZV)-specific peak T helper 1 (VZV-Th1) responses to ZVL were independently predicted by prevaccination VZV-Th1 responses, regulatory T cells (Treg), and PD1-expressing immune checkpoint T cells (Tcheck) but not by the age of the vaccinee. Persistence of VZV-Th1 1 year after vaccination was independently predicted by the factors mentioned above, by peak VZV-Th1 responses to ZVL, and by the age of the vaccinee. We further demonstrated by ex vivo blocking experiments the mechanistic role of PD1 and CTLA4 as modulators of decreased VZV-Th1 responses in the study participants. VZV-specific cytotoxic T cell (VZV-CTL) and T follicular helper responses to ZVL did not correlate with age, but similar to other Th1 responses, VZV-CTL peak and baseline responses were independently correlated. These data expand our understanding of the factors affecting the magnitude and kinetics of T cell responses to ZVL in older adults and show the importance of prevaccination Treg and Tcheck in modulating the immunogenicity of ZVL. This presents new potential interventions to increase vaccine responses in older adults. IMPORTANCE Vaccination is the most effective method to protect older adults against viral infections. However, the immunogenicity of viral vaccines in older adults is notoriously poor. The live attenuated zoster vaccine (ZVL) provides the best example of a gradual decrease of vaccine immunogenicity with every 10-year age increase above 50 years. Here we show that the abundance of regulatory T cells before vaccine administration to older adults has a significant inhibitory effect on immune responses to ZVL and, together with baseline immunity to varicella-zoster virus, explains the effect of age on the immunogenicity of ZVL. Moreover, in vitro blockade of regulatory T cell mechanisms of action with biologic modulators restores immune responses to varicella-zoster virus in vaccinees. Collectively, these observations suggest that immune modulators that block regulatory T cell activity may increase responses to viral attenuated vaccines in older adults.

scholarly journals Regulatory T-cell: Regulator of Host Defense in Infection

2017 ◽  
Vol 7 (1) ◽  
pp. 9 ◽  
Author(s):  
Mousa Mohammadnia-Afrouzi ◽  
Mehdi Shahbazi ◽  
Sedigheh Baleghi Damavandi ◽  
Ghasem Faghanzadeh Ganji ◽  
Soheil Ebrahimpour
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Regulatory T Cell ◽  
Critical Role ◽  
The Body ◽  
Cell Contact ◽  
Infectious Agents ◽  
Activated T Cells

Based on diverse activities and production of several cytokines, T lymphocytes and T helper cells are divided into Th1, Th2, Th17 and regulatory T-cell (T regs) subsets based on diverse activities and production of several cytokines. Infectious agents can escape from host by modulation of immune responses as effector T-cells and Tregs. Thus, regulatory T-cells play a critical role in suppression of immune responses to infectious agents such as viruses, bacteria, parasites and fungi and as well as preserving immune homeostasis. However, regulatory T-cell responses can advantageous for the body by minimizing the tissue-damaging effects. The following subsets of regulatory T-cells have been recognized: natural regulatory Tcells, Th3, Tr1, CD8+ Treg, natural killer like Treg (NKTreg) cells. Among various markers of Treg cells, Forkhead family transcription factor (FOXP3) as an intracellular protein is used for discrimination between activated T reg cells and activated T-cells. FOXP3 has a central role in production, thymocyte differentiation and function of regulatory Tcells. Several mechanisms have been indicated in regulation of T reg cells. As, the suppression of T-cells via regulatory T-cells is either mediated by Cell-cell contact and Immunosuppressive cytokines (TGF-Beta, IL-10) mediated.

scholarly journals Varicella-Zoster Virus–Specific Cellular Immune Responses to the Live Attenuated Zoster Vaccine in Young and Older Adults

2017 ◽  
Vol 199 (2) ◽  
pp. 604-612 ◽  
Author(s):  
Adriana Weinberg ◽  
Jennifer Canniff ◽  
Nadine Rouphael ◽  
Aneesh Mehta ◽  
Mark Mulligan ◽  
...  
Keyword(s):  
Older Adults ◽  
Immune Responses ◽  
Varicella Zoster Virus ◽  
Zoster Vaccine ◽  
Varicella Zoster ◽  
Cellular Immune Responses ◽  
Cellular Immune

scholarly journals Influence of Frequent Infectious Exposures on General and Varicella-Zoster Virus-Specific Immune Responses in Pediatricians

2014 ◽  
Vol 21 (3) ◽  
pp. 417-426 ◽  
Author(s):  
Benson Ogunjimi ◽  
Evelien Smits ◽  
Steven Heynderickx ◽  
Johan Van den Bergh ◽  
Joke Bilcke ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Varicella Zoster Virus ◽  
Humoral Immunity ◽  
Interleukin 2 ◽  
Effector Memory ◽  
Varicella Zoster ◽  
Early Protein ◽  
Ifn Γ

ABSTRACTReexposure to viruses is assumed to strengthen humoral and cellular immunity via the secondary immune response. We studied the effects of frequent exposure to viral infectious challenges on immunity. Furthermore, we assessed whether repetitive exposures to varicella-zoster virus (VZV) elicited persistently high immune responses. Blood samples from 11 pediatricians and matched controls were assessed at 3 time points and 1 time point, respectively. Besides the assessment of general immunity by means of measuring T-cell subset percentages, antibody titers and gamma interferon (IFN-γ)/interleukin 2 (IL-2)-producing T-cell percentages against adenovirus type 5 (AdV-5), cytomegalovirus (CMV), tetanus toxin (TT), and VZV were determined. Pediatricians had lower levels of circulating CD4+-naive T cells and showed boosting of CD8+effector memory T cells. Although no effect on humoral immunity was seen, repetitive exposures to VZV induced persistently higher percentages of IFN-γ-positive T cells against all VZV antigens tested (VZV glycoprotein E [gE], VZV intermediate-early protein 62 [IE62], and VZV IE63) than in controls. T cells directed against latency-associated VZV IE63 benefitted the most from natural exogenous boosting. Although no differences in cellular or humoral immunity were found between the pediatricians and controls for AdV-5 or TT, we did find larger immune responses against CMV antigens in pediatricians. Despite the high infectious burden, we detected a robust and diverse immune system in pediatricians. Repetitive exposures to VZV have been shown to induce a stable increased level of VZV-specific cellular but not humoral immunity. Based on our observations, VZV IE63 can be considered a candidate for a zoster vaccine.

scholarly journals Formaldehyde exposure induces regulatory T cell-mediated immunosuppression via calcineurin-NFAT signalling pathway

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jeongsik Park ◽  
Hyo-Seon Yang ◽  
Mi-Kyung Song ◽  
Dong Im Kim ◽  
Kyuhong Lee
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Mrna Expression ◽  
Regulatory T Cell ◽  
Cell Activity ◽  
Helper T Cells ◽  
Dependent Manner ◽  
Dose Dependent

Abstract In this study, we investigated the effects of Formaldehyde (FA) exposure on splenic immune responses wherein helper T cells become activated and differentiate into effector T and regulatory T cells. BALB/c mice were exposed to two FA concentrations (1.38 mg/m3 and 5.36 mg/m3) for 4 h/day and 5 days/week for 2 weeks. FA-induced immune responses were examined by the production of cytokines, expression of mRNAs, and distributions of helper T cells and regulatory T cells. Moreover, expression of calcineurin and NFATs, regulatory T cell-related signalling proteins, were evaluated. FA exposure suppressed Th2-, Th1-, and Th17-related splenic cytokines in a dose-dependent manner. mRNA expression of splenic cytokines was also decreased by FA exposure, which correlated with decreased cytokine expression. In parallel, FA exposure promoted T cell differentiation into regulatory T cells in a dose-dependent manner supported by the expression of calcineurin and NFAT1. Taken together, our results indicated that FA exposure increases the number of regulatory T cells via calcineurin-NFAT signalling, thereby leading to effector T cell activity suppression with decreased T cell-related cytokine secretion and mRNA expression. These findings provide insight into the mechanisms underlying the adverse effects of FA and accordingly have general implications for human health, particularly in occupational settings.

Anti-CD20 therapy corrects a CD8 regulatory T cell deficit in multiple sclerosis

2021 ◽  
pp. 135245852110033
Author(s):  
Quentin Howlett-Prieto ◽  
Xuan Feng ◽  
John F Kramer ◽  
Kevin J Kramer ◽  
Timothy W Houston ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
B Cell ◽  
Regulatory T Cell ◽  
Healthy Controls ◽  
Regulatory Cells ◽  
Long Term Treatment ◽  
Anti Cd20

Objective: To determine the effect of long-term anti-CD20 B-cell-depleting treatment on regulatory T cell immune subsets that are subnormal in untreated MS patients. Methods: 30 clinically stable MS patients, before and over 38 months of ocrelizumab treatment, were compared to 13 healthy controls, 29 therapy-naïve MS, 9 interferon-β-treated MS, 3 rituximab-treated MS, and 3 rituximab-treated patients with other autoimmune inflammatory diseases. CD8, CD28, CD4, and FOXP3 expression in peripheral blood mononuclear cells was quantitated with flow cytometry. Results: CD8+ CD28− regulatory cells rose from one-third of healthy control levels before ocrelizumab treatment (2.68% vs 7.98%), normalized by 12 months (13.5%), and rose to 2.4-fold above healthy controls after 18 months of ocrelizumab therapy (19.0%). CD4+ FOXP3+ regulatory cells were lower in MS than in healthy controls (7.98%) and showed slight long-term decreases with ocrelizumab. CD8+ CD28− and CD4+ FOXP3+ regulatory T cell percentages in IFN-β-treated MS patients were between those of untreated MS and healthy controls. Interpretation: Long-term treatment with ocrelizumab markedly enriches CD8+ CD28− regulatory T cells and corrects the low levels seen in MS before treatment, while slightly decreasing CD4+ FOXP3+ regulatory T cells. Homeostatic enrichment of regulatory CD8 T cells provides a mechanism, in addition to B cell depletion, for the benefits of anti-CD20 treatment in MS.

scholarly journals Regulatory T Cells Contribute to Resistance against Lyme Arthritis

2020 ◽  
Vol 88 (11) ◽  
Author(s):  
Emily M. Siebers ◽  
Elizabeth S. Liedhegner ◽  
Michael W. Lawlor ◽  
Ronald F. Schell ◽  
Dean T. Nardelli
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lyme Disease ◽  
Regulatory T Cells ◽  
Regulatory T Cell ◽  
Interleukin 10 ◽  
Lyme Arthritis ◽  
Interleukin 17 ◽  
Content Type

ABSTRACT The symptoms of Lyme disease are caused by inflammation induced by species of the Borrelia burgdorferi sensu lato complex. The various presentations of Lyme disease in the population suggest that differences exist in the intensity and regulation of the host response to the spirochete. Previous work has described correlations between the presence of regulatory T cells and recovery from Lyme arthritis. However, the effects of Foxp3-expressing CD4+ T cells existing prior to, and during, B. burgdorferi infection have not been well characterized. Here, we used C57BL/6 “depletion of regulatory T cell” mice to assess the effects these cells have on the arthritis-resistant phenotype characteristic of this mouse strain. We showed that depletion of regulatory T cells prior to infection with B. burgdorferi resulted in sustained swelling, as well as histopathological changes, of the tibiotarsal joints that were not observed in infected control mice. Additionally, in vitro stimulation of splenocytes from these regulatory T cell-depleted mice resulted in increases in gamma interferon and interleukin-17 production and decreases in interleukin-10 production that were not evident among splenocytes of infected mice in which Treg cells were not depleted. Depletion of regulatory T cells at various times after infection also induced rapid joint swelling. Collectively, these findings provide evidence that regulatory T cells existing at the time of, and possibly after, B. burgdorferi infection may play an important role in limiting the development of arthritis.

scholarly journals Thymic Regulatory T Cell Development: Role of Signalling Pathways and Transcription Factors

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Mark Engel ◽  
Tom Sidwell ◽  
Ajithkumar Vasanthakumar ◽  
George Grigoriadis ◽  
Ashish Banerjee
Keyword(s):  
T Cells ◽  
Transcription Factors ◽  
T Cell ◽  
Regulatory T Cells ◽  
Immune Tolerance ◽  
Regulatory T Cell ◽  
T Cell Development ◽  
Signalling Pathways ◽  
Treg Development

Regulatory T cells (Tregs) are a subset of CD4 T cells that are key mediators of immune tolerance. Most Tregs develop in the thymus. In this review we summarise recent findings on the role of diverse signalling pathways and downstream transcription factors in thymic Treg development.

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