The characterization and role of regulatory T cells in immune reactions

Jacek, R. Wilczynski

doi:10.2741/2840

Cited by 72 publications

(55 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Therefore, electrophysiology tests demonstrated recovery of hearing to click stimulus and a wide range of specific frequencies 5 weeks after IL-10 gene transfer. 37,38 In this study, our overall aim was to define the role of both endogenous and exogenous IL-10 in the setting of b-tubulin-induced EAHL. In our study, EAHL developed progressively in b-tubulin-immunized IL-10 À/À mice throughout the experiment, and the hearing loss lasted at least 9 weeks after immunization.…”

Section: Resultsmentioning

confidence: 99%

Experimental autoimmune hearing loss is exacerbated in IL-10-deficient mice and reversed by IL-10 gene transfer

et al. 2011

View full text Add to dashboard Cite

Interleukin-10 (IL-10) has an important role in the homeostatic regulation of autoreactive T-cell repertoire. We hypothesized that endogenous IL-10 would regulate the severity of b-tubulin-induced experimental autoimmune hearing loss (EAHL) and that exogenous IL-10 would abrogate it. BALB/c wild-type (WT) and homozygous IL-10-deficient mice (IL-10 À/À ) underwent b-tubulin immunization to develop EAHL; some IL-10 mice with EAHL were administered IL-10 DNA at the peak of EAHL. Auditory brainstem responses were examined over time. EAHL developed progressively in both WT and IL-10 À/À mice. However, the severity of hearing loss in the IL-10 À/À mice was significantly greater than that in WT animals. Moreover, disease severity was associated with a significantly enhanced interferon-g level and loss of hair cells in IL-10 À/À mice. IL-10 administered to EAHL IL-10 À/À mice promoted IL-10 expression. Consequently, hearing significantly improved by protecting hair cells in established EAHL. Importantly, IL-10 treatment suppressed proliferation of antigen-specific T-helper type 1 (Th1) cells, and the suppression can be attributed to inducing IL-10-secreting regulatory T cells that suppressed autoreactive T cells. We demonstrated that the lack of IL-10 exacerbated hearing loss, and the exogenous administration of IL-10 improved hearing. Mechanistically, our results indicate that IL-10 is capable of controlling autoimmune reaction severity by suppressing Th1-type proinflammatory responses and inducing IL-10-secreting regulatory T cells.

show abstract

Section: Resultsmentioning

confidence: 99%

Experimental autoimmune hearing loss is exacerbated in IL-10-deficient mice and reversed by IL-10 gene transfer

et al. 2011

View full text Add to dashboard Cite

show abstract

“…The T R -1 cells exhibit a short life in periphery [53]. Thus, a transient secretion of IL-10 upon treatment with a single dose of DEF reagents may explain the relatively short therapeutic effect (e.g.…”

Section: Discussionmentioning

confidence: 99%

Reversal of type 1 diabetes by a new MHC II‐peptide chimera: “Single‐epitope‐mediated suppression” to stabilize a polyclonal autoimmune T‐cell process

et al. 2010

View full text Add to dashboard Cite

Polyclonality of self-reactive CD41 T cells is the hallmark of several autoimmune diseases like type 1 diabetes. We have previously reported that a soluble dimeric MHC II-peptide chimera prevents and reverses type 1 diabetes induced by a monoclonal diabetogenic T-cell population in double Tg mice [Casares, S. et al., Nat. Immunol. 2002. 3: 383-391].Since most of the glutamic acid decarboxylase 65 (GAD65)-specific CD4 1 T cells in the NOD mouse are tolerogenic but unable to function in an autoimmune environment, we have activated a silent, monoclonal T-regulatory cell population (GAD65 217-230 -specific CD4 1 T cells) using a soluble I-A ab g7 /GAD65 217-230 /Fcg2a dimer, and measured the effect on the ongoing polyclonal diabetogenic T-cell process. Activated GAD65 217-230 -specific T cells and a fraction of the diabetogenic (B 9-23 -specific) T cells were polarized toward the IL-10-secreting T-regulatory type 1-like function in the pancreas of diabetic NOD mice. More importantly, this led to the reversal of hyperglycemia for more than 2 months post-therapy in 80% of mice in the context of stabilization of pancreatic insulitis and improved insulin secretion by the b cells. These findings argue for the stabilization of a polyclonal selfreactive T-cell process by a single epitope-mediated bystander suppression. Dimeric MHC class II-peptide chimeras-like approach may provide rational grounds for the development of more efficient antigen-specific therapies in type 1 diabetes.

show abstract

“…It is also reasonable, however, that because of their great heterogeneity and plasticity, certain liver-infiltrating T cells, conditioned by the local cytokine milieu, may develop phenotypes which may favour fibrogenesis. Moreover, as a result of an aberrant activation mechanism during HCV-associated chronic inflammation, certain HCV-specific T cells displaying a regulatory phenotype, can differentiate in the liver from naive CD4 + T cells, being able to inappropriately inhibit the anti-viral immune response (6,7). Further studies are required to investigate the interplay between thymus-derived natural Tregs and peripherally-induced Tregs.…”

mentioning

confidence: 99%

“…Tregs have been shown to exhibit a relevant heterogeneity in their differentiation patterns, mechanisms of action, tissue distribution as well as phenotype presentation (4)(5)(6). However, the main Treg subset is believed to be comprised of the CD4 + T cell subset expressing high levels of CD25 (CD25 hi ) and the transcription factor forkhead box protein 3 (Foxp3) (natural Tregs).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of circulating CD4+CD25+ and liver-infiltrating Foxp3+ cells in HCV-associated liver disease

et al. 2012

View full text Add to dashboard Cite

Abstract. In hepatitis C virus (HCV)-associated liver disease, the immune system is unable to clear the viral infection. Previous studies have raised the possibility of an involvement of regulatory T cells (Tregs) + cells in the liver infiltrates showed significantly higher proportions of peripheral CD4 + CD25 low cells. Moreover, we found lower serum transaminase levels in the patients than in the controls, as shown by Foxp3 + immunohistochemistry, although these results were only statistically significant as regards alanine transaminase (ALT). In conclusion, these data suggest that the presence of Tregs infiltrating the liver is associated with high levels of activated/effector T cells in the peripheral blood and lower activity of hepatitis. Therefore, liver-infiltrating Tregs may play a role in limiting tissue damage and may thus support an effective immune response against HCV.

show abstract

The characterization and role of regulatory T cells in immune reactions

Cited by 72 publications

References 91 publications

Experimental autoimmune hearing loss is exacerbated in IL-10-deficient mice and reversed by IL-10 gene transfer

Experimental autoimmune hearing loss is exacerbated in IL-10-deficient mice and reversed by IL-10 gene transfer

Reversal of type 1 diabetes by a new MHC II‐peptide chimera: “Single‐epitope‐mediated suppression” to stabilize a polyclonal autoimmune T‐cell process

Evaluation of circulating CD4+CD25+ and liver-infiltrating Foxp3+ cells in HCV-associated liver disease

Contact Info

Product

Resources

About