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

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.

Impact of Immune-Modulatory Drugs on Regulatory T Cell

“…However, high-dose ATG impairs thymic generation of Tconv and Treg cells in allogeneic hematopoietic stem cell transplantation 34,35 . ATG therapy may also modulate antigen-specific immune responses by inducing memory-like Treg, as well as other protective T cells such as Th2 and IL-10-producing Tr1 cells 36 . Thus, immunological impact of ATG is not only limited to T cell depletion, but also in relative preservation of Treg especially at lower doses.…”

Murder in the Cathedral: Antibodies and the Limits of Transplantation

“…(42) In addition, ATG may increase regulatory T cell (T reg ), offering the opportunity of endogenous control of the immunological response. (43) Retrospective analysis of the CMJAH LpAMR cohort has, however, failed to demonstrate a beneficial effect for ATG. (40) Indeed, prescription of ATG in this cohort was associated with increased risk of graft loss compared to the use of either Rituximab (40) (Figure 3).…”

Immune Relevant and Immune Deficient Mice: Options and Opportunities in Translational Research

“…216,[224][225][226] Anti-thymocyte globulin (ATG), is another important immunosuppressive agent that specifically depletes T cells from peripheral blood and lymphoid organs in NOD mice; it is also used in the modulation of graft rejection and autoimmune disorders in mice. 227,228 Glucans, CpG oligodeoxynucleotides (CpG ODN) and bacterial enterotoxins have been used as prophylactic or therapeutic interventions to modify immune responses to infections or vaccination, or to counteract effects of immunotoxic agents (see Table 4). 229,230 Surgical Thymectomy or splenectomy are the traditional surgical methods to alter immunity.…”