Induction of self-antigen-specific Foxp3+ regulatory T cells in the periphery by lymphodepletion treatment with anti-mouse thymocyte globulin in mice

Yan Lu, Jun Suzuki, Maria Guillioli, Oliver Umland, Zhibin Chen

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Lymphodepletion therapies are increasingly tested for controlling immune damage. One appealing premise for such a therapy is that it may 'reboot' the immune system and restore immune tolerance. However, the tolerogenic potential of lymphodepletion therapies remains controversial. The debate is exemplified by conflicting evidence from the studies of anti-thymocyte globulin (ATG), a prototype of immunodepleting drugs, in particular on whether it induces CD4+CD25+Foxp3+ regulatory T (Treg) cells. To understand the impact of ATG on T cells at a clonal level in vivo, we studied the effect of anti-mouse thymocyte globulin (mATG) in a reductionist model in which the T-lymphocyte repertoire consists of a single clone of pathogenic T effector (Teff) cells specific to a physiological self-antigen. The mATG treatment led to peripheral induction of antigen-specific Treg cells from an otherwise monoclonal Teff repertoire, independent of thymic involvement. The de novo induction of Treg cells occurred consistently in local draining lymph nodes, and persistence of induced Treg cells in blood correlated with long-term protection from autoimmune destruction. This study provides in vivo evidence for clonal conversion from a pathogenic self-antigen-specific Teff cell to a Treg cell in the setting of immunodepletion therapies.

Original languageEnglish (US)
Pages (from-to)50-59
Number of pages10
JournalImmunology
Volume134
Issue number1
DOIs
StatePublished - Sep 2011

Keywords

  • Autoimmunity
  • CD4 T cells
  • Immunotherapeutics
  • Regulatory T cells
  • Tolerance

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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