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Published online before print May 13, 2005

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0105050

Received for publication January 25, 2005.

Accepted for publication April 11, 2005.

Article

T cell homeostasis in tolerance and immunity

Department of Immunology, The Scripps Research Institute, La Jolla, California

^@ To whom correspondence should be addressed. E-mail: noras{at}scripps.edu.

	Abstract

The size of the peripheral T cell pool is remarkably stable throughout life, reflecting precise regulation of cellular survival, proliferation, and apoptosis. Homeostatic proliferation refers to the process by which T cells spontaneously proliferate in a lymphopenic host. The critical signals driving this expansion are "space," contact with self-major histocompatibility complex (MHC)/peptide complexes, and cytokine stimulation. A number of studies have delineated an association between T cell lymphopenia, compensatory homeostatic expansion, and the development of diverse autoimmune syndromes. In the nonobese diabetic mouse model of type 1 diabetes, lymphopenia-induced homeostatic expansion fuels the generation of islet-specific T cells. Excess interleukin-21 facilitates T cell cycling but limited survival, resulting in recurrent stimulation of T cells specific for self-peptide/MHC complexes. Indeed, data from several experimental models of autoimmunity indicate that a full T cell compartment restrains homeostatic expansion of self-reactive cells, which could otherwise dominate the repertoire. This review describes the mechanisms that govern T cell homeostatic expansion and outlines the evidence that lymphopenia presents a risk for development of autoimmune disease.

Key Words: homeostatic proliferation • lymphopenia • autoimmunity • nonobese diabetic mouse

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