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Open Access Highly Accessed Research article

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

Chang-Qing Xia12*, Anna V Chernatynskaya2, Clive H Wasserfall2, Suigui Wan1, Benjamin M Looney2, Scott Eisenbeis3, John Williams3, Michael J Clare-Salzler2 and Mark A Atkinson2

Author Affiliations

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

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BMC Immunology 2012, 13:70  doi:10.1186/1471-2172-13-70

Published: 14 December 2012

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.

Keywords:
Anti-thymocyte globulin; Naïve and memory T cells; Regulatory T cells; T helper cell; Autoimmune diabetes; Nonobese diabetic mouse