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

• Published in: BMC immunology Vol. 13; no. 1; p. 70
• 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: Journal Article
• Language: English
• Published: England BioMed Central 14.12.2012; BioMed Central Ltd; BMC
• Subjects: Animals; Anti-thymocyte globulin; Antibodies - pharmacology; Antilymphocyte Serum - administration & dosage; Antilymphocyte Serum - pharmacology; Autoantigens - immunology; Autoimmune diabetes; Blood; CD3 Complex - immunology; Cell Proliferation - drug effects; Cloning; Cross-Priming - drug effects; Cross-Priming - immunology; Cytokines; Diabetes; Experiments; Female; Flow cytometry; Forkhead Transcription Factors - metabolism; Immune system; Immunoglobulin G - immunology; Immunologic Memory - drug effects; Immunology; Interleukin-10 - biosynthesis; L-Selectin - metabolism; Lymphocyte Count; Lymphocyte Depletion; Lymphocytes; Lymphoid Tissue - drug effects; Lymphoid Tissue - immunology; Mice; Mice, Inbred NOD; Nanoparticles; Naïve and memory T cells; Nonobese diabetic mouse; Receptors, Antigen, T-Cell - metabolism; Regulatory T cells; Rodents; Spleen; Spleen - drug effects; Spleen - immunology; Studies; T helper cell; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; Th1 Cells - drug effects; Th1 Cells - immunology; Th2 Cells - drug effects; Th2 Cells - immunology
• ISSN: 1471-2172; 1471-2172
• DOI: 10.1186/1471-2172-13-70

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. 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. 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.