Abstract

BackgroundATG 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 studyIn 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.ResultsPeripheral 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.ConclusionATG 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.

Highlights

  • Anti-thymocyte globulin (ATG) has been employed to deplete T cells in several immune-mediated conditions

  • ATG therapy efficiently depletes T cells from peripheral blood, but is less efficient in depleting T cells from lymphoid organs It is known that ATG therapy can largely eliminate T cells from peripheral blood

  • Our kinetic observation of peripheral blood cells post-ATG therapy revealed that both the CD4+ and CD8+ T cells dropped to their lowest levels at day 3 post-ATG therapy and by day 22, peripheral blood CD4+ T cells returned to normal levels

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Summary

Introduction

ATG has been employed to deplete T cells in several immune-mediated conditions. 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. Anti-thymocyte globulin (ATG), trade name thymoglobulinW, has been employed for decades as an immune modulator for a variety of clinical indications It is currently one of the most common immunosuppressive reagents used in allogeneic transplantation [1,2,3] and more recently, in the treatment of a variety of autoimmune disorders [4,5,6,7,8]. Recent data and lymph nodes post-ATG therapy, focusing on addressing the questions of how ATG therapy affected naive and memory T cells, including naïve and memory Tregs. These strains were utilized due to their common utilization in studies of murine ATG efficacy for type 1 diabetes, as well as the ability to utilize mice having a defined antigenic specificity.

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