Journal
SCIENCE
Volume 322, Issue 5899, Pages 271-275Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1160062
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- Ministry of Education, Sports and Culture of Japan, Japan Science and Technology Agency [Grants-in-Aid]
- Japan Society for the Promotion of Science
- Astra-Zeneca, Loughborough, UK
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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.
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