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T cell homeostasis in tolerance and immunity
Author(s) -
Marleau Annette M.,
Sarvetnick Nora
Publication year - 2005
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0105050
Subject(s) - biology , homeostasis , major histocompatibility complex , microbiology and biotechnology , t cell , autoimmunity , immunology , immune system
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.