T cell homeostasis in tolerance and immunity.
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 that 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.
Marleau
Annette M
AM
The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Sarvetnick
Nora
N
D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D006649:Histocompatibility Antigens / Q000276:immunology; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D007378:Interleukins / Q000276:immunology; D008231:Lymphopenia / Q000276:immunology*; D017634:Self Tolerance / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D000098546:Interleukin-21
D016207:Cytokines; D006649:Histocompatibility Antigens; D007378:Interleukins; D000098546:Interleukin-21