CD4+CD25+ immune regulatory cells are required for induction of tolerance to alloantigen via costimulatory blockade

Patricia A. Taylor, Randolph J. Noelle, Bruce R. Blazar

Research output: Contribution to journalArticle

467 Scopus citations

Abstract

Immune regulatory CD4+CD25+ cells play a vital role in the induction and maintenance of self-tolerance and are essential for T cell homeostasis and the prevention of autoimmunity. Induction of tolerance to allogeneic donor grafts is a clinically desirable goal in bone marrow and solid organ transplantation. To determine whether CD4+CD25+ cells regulate T cell responses to alloantigen and are critical for tolerance induction, murine CD4+ T cells were tolerized to alloantigen via ex vivo CD40 ligand (CD40L)/CD40 or CD28/cytotoxic T lymphocyte-associated antigen 4/B7 blockade resulting in secondary mixed leukocyte reaction hyporesponsiveness and tolerance to alloantigen in vivo. CD4+CD25+ T cells were found to be potent regulators of alloresponses. Depletion of CD4+CD25+ T cells from the CD4+ responder population completely abrogated ex vivo tolerance induction to alloantigen as measured by intact responses to alloantigen restimulation in vitro and in vivo. Addback of CD4+CD25+ T cells to CD4+CD25- cultures restored tolerance induction. These data are the first to indicate that CD4+CD25+ cells are essential for the induction of tolerance to alloantigen and have important implications for tolerance-inducing strategies targeted at T cell costimulatory pathways.

Original languageEnglish (US)
Pages (from-to)1311-1317
Number of pages7
JournalJournal of Experimental Medicine
Volume193
Issue number11
DOIs
StatePublished - Jun 4 2001

Keywords

  • IL-2 receptor α chain (CD25)
  • In vivo animal models
  • Regulatory T cell
  • Tolerance
  • Transplantation

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