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Nat Immunol. 2003 Jul;4(7):664-9. Epub 2003 May 25.

The inhibitory function of B7 costimulators in T cell responses to foreign and self-antigens.

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1
Department of Pathology, University of California San Francisco School of Medicine, San Francisco, California 94143-0511, USA.

Abstract

When antigen-presenting cells (APCs) encounter inflammatory stimuli, they up-regulate their expression of B7. A small amount of B7 is also constitutively expressed on resting APCs, but its function is unclear. Here we show that initiation of T cell responses requires the expression of B7 on immunizing APCs, but the responses are much greater in the absence of basal B7 expression. Transfer of antigen-specific CD4+CD25+ cells reverses the increased responsiveness, and tolerance to a self-protein is broken by immunization in the absence of basal B7, thereby inducing autoimmunity. Similar loss of self-tolerance is seen on depletion of CD25+ cells. Thus, constitutively expressed B7 costimulators function to suppress T cell activation and maintain self-tolerance, principally by sustaining a population of regulatory T cells.

PMID:
12766766
DOI:
10.1038/ni939
[Indexed for MEDLINE]
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