Anti-thymocyte globulin (ATG) prevents autoimmune encephalomyelitis by expanding myelin antigen-specific Foxp3+ regulatory T cells

Denise T. Chung, Thomas Korn, Julie Richard, Melanie Ruzek, Adam P. Kohm, Stephen Miller, Sharon Nahill, Mohamed Oukka*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

The T cell-depleting polyclonal antibody, anti-thymocyte globulin (ATG) has long been used in organ transplantation to treat acute rejection episodes. More recently, it is also being used as part of an induction regimen to protect allografts. It has been proposed that ATG might deplete effector T cells (T-effs) while sparing regulatory T cells (T-regs). In order to test whether ATG is effective in autoimmune disease, we used Foxp3gfp 'knock-in' mice in combination with a myelin oligodendrocyte glycoprotein (MOG)35-55/IAb tetramer to study more closely the effect of ATG treatment on antigen-specific T cell responses in vivo during MOG-induced experimental autoimmune encephalomyelitis (EAE), an animal model for Multiple Sclerosis. ATG treatment enhanced the expansion of MOG-specific T-regs (CD4+Foxp3+) in MOG-immunized mice. T-effs were depleted, but on a single-cell basis, the effector function of residual T-effs was not compromised by ATG. Thus, ATG tipped the balance of T-effs and T-regs and skewed an auto-antigen-specific immune reaction from a pathogenic T cell response to a potentially protective T-reg response. In both acute and relapsing remitting disease models, ATG treatment resulted in the attenuation from EAE, both in a preventive and early therapeutic setting. We conclude that ATG treatment enforces the development of a dominant immunoregulatory environment which may be advantageous for the treatment of T cell-driven autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)1003-1010
Number of pages8
JournalInternational Immunology
Volume19
Issue number8
DOIs
StatePublished - Aug 2007

Keywords

  • Anti-thymocyte globulin
  • Antigen-specific
  • EAE
  • Multiple sclerosis
  • T-reg cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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