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

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• 作者：Chang-Qing Xia (1) (2)
  Anna V Chernatynskaya (2)
  Clive H Wasserfall (2)
  Suigui Wan (1)
  Benjamin M Looney (2)
  Scott Eisenbeis (3)
  John Williams (3)
  Michael J Clare-Salzler (2)
  Mark A Atkinson (2)
  
• 关键词：Anti ; thymocyte globulin ; Na?ve and memory T cells ; Regulatory T cells ; T helper cell ; Autoimmune diabetes ; Nonobese diabetic mouse
• 刊名：BMC Immunology
• 出版年：2012
• 出版时间：December 2012
• 年：2012
• 卷：13
• 期：1
• 全文大小：2256KB
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• 作者单位：Chang-Qing Xia (1) (2)
  Anna V Chernatynskaya (2)
  Clive H Wasserfall (2)
  Suigui Wan (1)
  Benjamin M Looney (2)
  Scott Eisenbeis (3)
  John Williams (3)
  Michael J Clare-Salzler (2)
  Mark A Atkinson (2)
  
  1. Department of Hematology, Xuanwu Hospital, Capital Medical University, #45 Changchun Street, Xicheng District, Beijing, P.R. China
  2. Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, 32610, USA
  3. Genzyme Corporation, Framingham, MA, 02142, USA
  
• ISSN：1471-2172

文摘

Background ATG has been employed to deplete T cells in several immune-mediated conditions. However, whether ATG administration affects na?ve 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 na?ve 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.