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

Science (New York, N.Y.) | Oct 10, 2008

http://www.ncbi.nlm.nih.gov/pubmed/18845758

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 RIS Download

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

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