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CTLA-4 control over Foxp3+ regulatory T cell function.

Naturally occurring Foxp3+CD4+ regulatory T cells (Tregs) are essential for maintaining immunological self-tolerance and immune homeostasis. Here, we show that a specific deficiency of cytotoxic T lymphocyte antigen 4 (CTLA-4) in Tregs results in spontaneous development of systemic lymphoproliferation, fatal T cell-mediated autoimmune disease, and hyperproduction of immunoglobulin E in mice, and it also produces potent tumor immunity. Treg-specific CTLA-4 deficiency impairs in vivo and in vitro suppressive function of Tregs-in particular, Treg-mediated down-regulation of CD80 and CD86 expression on dendritic cells. Thus, natural Tregs may critically require CTLA-4 to suppress immune responses by affecting the potency of antigen-presenting cells to activate other T cells.

Pubmed ID: 18845758


  • Wing K
  • Onishi Y
  • Prieto-Martin P
  • Yamaguchi T
  • Miyara M
  • Fehervari Z
  • Nomura T
  • Sakaguchi S


Science (New York, N.Y.)

Publication Data

October 10, 2008

Associated Grants


Mesh Terms

  • Animals
  • Antigen-Presenting Cells
  • Antigens, CD
  • Antigens, CD80
  • Antigens, CD86
  • Autoimmune Diseases
  • Autoimmunity
  • CD8-Positive T-Lymphocytes
  • CTLA-4 Antigen
  • Dendritic Cells
  • Down-Regulation
  • Female
  • Forkhead Transcription Factors
  • Immune Tolerance
  • Immunoglobulin E
  • Immunoglobulin G
  • Leukemia
  • Lymphocyte Activation
  • Lymphocytes
  • Male
  • Mice
  • Mice, Inbred BALB C
  • T-Lymphocytes, Regulatory