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

• Main Authors: Xia Chang-Qing, Chernatynskaya Anna V, Wasserfall Clive H, Wan Suigui, Looney Benjamin M, Eisenbeis Scott, Williams John, Clare-Salzler Michael J, Atkinson Mark A
• Format: Article
• Language: English
• Published: BMC 2012-12-01
• Series: BMC Immunology
• Subjects: Anti-thymocyte globulin; Naïve and memory T cells; Regulatory T cells; T helper cell; Autoimmune diabetes; Nonobese diabetic mouse
• Online Access: http://www.biomedcentral.com/1471-2172/13/70

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>The context and purpose of the study</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p>