T cell homeostasis in tolerance and immunity

Annette M. Marleau, Nora Sarvetnick

Research output: Contribution to journalReview articlepeer-review

103 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)575-584
Number of pages10
JournalJournal of Leukocyte Biology
Issue number3
StatePublished - Sep 2005
Externally publishedYes


  • Autoimmunity
  • Homeostatic proliferation
  • Lymphopenia
  • Nonobese diabetic mouse

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology


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