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Anti-thymocyte globulin (ATG) differentially depletes naive and memory T cells and permits memory-type regulatory T cells in nonobese diabetic mice.


ABSTRACT:

Background

ATG has been employed to deplete T cells in several immune-mediated conditions. However, whether ATG administration affects naïve and memory T cell differently is largely unknown. THE CONTEXT AND PURPOSE OF THE STUDY: In this study, we assessed how murine ATG therapy affected T cell subsets in NOD mice, based on their regulatory and naïve or memory phenotype, as well as its influence on antigen-specific immune responses.

Results

Peripheral blood CD4+ and CD8+ T cells post-ATG therapy declined to their lowest levels at day 3, while CD4+ T cells returned to normal levels more rapidly than CD8+ T cells. ATG therapy failed to eliminate antigen-primed T cells. CD4+ T cell responses post-ATG therapy skewed to T helper type 2 (Th2) and possibly IL-10-producing T regulatory type 1 (Tr1) cells. Intriguingly, Foxp3+ regulatory T cells (Tregs) were less sensitive to ATG depletion and remained at higher levels following in vivo recovery compared to controls. Of note, the frequency of Foxp3+ Tregs with memory T cell phenotype was significantly increased in ATG-treated animals.

Conclusion

ATG therapy may modulate antigen-specific immune responses through inducing memory-like regulatory T cells as well as other protective T cells such as Th2 and IL-10-producing Tr1 cells.

SUBMITTER: Xia CQ 

PROVIDER: S-EPMC3547787 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Publications

Anti-thymocyte globulin (ATG) differentially depletes naïve and memory T cells and permits memory-type regulatory T cells in nonobese diabetic mice.

Xia Chang-Qing CQ   Chernatynskaya Anna V AV   Wasserfall Clive H CH   Wan Suigui S   Looney Benjamin M BM   Eisenbeis Scott S   Williams John J   Clare-Salzler Michael J MJ   Atkinson Mark A MA  

BMC immunology 20121214


<h4>Background</h4>ATG has been employed to deplete T cells in several immune-mediated conditions. However, whether ATG administration affects naïve and memory T cell differently is largely unknown. THE CONTEXT AND PURPOSE OF THE STUDY: In this study, we assessed how murine ATG therapy affected T cell subsets in NOD mice, based on their regulatory and naïve or memory phenotype, as well as its influence on antigen-specific immune responses.<h4>Results</h4>Peripheral blood CD4+ and CD8+ T cells po  ...[more]

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