title: Anti-thymocyte globulin (ATG) differentially depletes naïve and memory T cells and permits memory-type regulatory T cells in nonobese diabetic mice.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing, P.R. China. cqx65@yahoo.com
authors.forename: Chang-Qing
authors.initials: CQ
authors.lastname: Xia
authors.forename: Anna V
authors.initials: AV
authors.lastname: Chernatynskaya
authors.forename: Clive H
authors.initials: CH
authors.lastname: Wasserfall
authors.forename: Suigui
authors.initials: S
authors.lastname: Wan
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Looney
authors.forename: Scott
authors.initials: S
authors.lastname: Eisenbeis
authors.forename: John
authors.initials: J
authors.lastname: Williams
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Clare-Salzler
authors.forename: Mark A
authors.initials: MA
authors.lastname: Atkinson
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000494:pharmacology*; D001324:Autoantigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D045142:Cross-Priming / Q000187:drug effects / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology; D007156:Immunologic Memory / Q000187:drug effects*; D016753:Interleukin-10 / Q000096:biosynthesis; D019041:L-Selectin / Q000378:metabolism; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008221:Lymphoid Tissue / Q000187:drug effects / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D000906:Antibodies; D000961:Antilymphocyte Serum; D001324:Autoantigens; D017252:CD3 Complex; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007074:Immunoglobulin G; D011948:Receptors, Antigen, T-Cell; D019041:L-Selectin; D016753:Interleukin-10