CTLA-4 control over Foxp3+ regulatory T cell function

Kajsa Wing, Yasushi Onishi, Paz Prieto-Martin, Tomoyuki Yamaguchi, Makoto Miyara, Zoltan Fehervari, Takashi Nomura, Shimon Sakaguchi

Research output: Contribution to journalArticlepeer-review

1818 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)271-275
Number of pages5
JournalScience
Volume322
Issue number5899
DOIs
Publication statusPublished - 2008 Oct 10

ASJC Scopus subject areas

  • General

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