Homeostatic expansion of T cells during immune insufficiency generates autoimmunity

Cecile King, Alex Ilic, Kersten Koelsch, Nora Sarvetnick

Research output: Contribution to journalArticle

531 Scopus citations

Abstract

During illness and stress, the immune system can suffer a considerable loss of T cells (lymphopenia). The remaining T cells undergo vigorous compensatory expansion, known as homeostatic proliferation, to reconstitute the immune system. Interestingly, human diseases of autoimmune etiology often present with immune deficiencies such as lymphopenia. In this study, we show that reduced T cell numbers and the resulting exaggerated homeostatic-type proliferation of T cells generate autoimmunity. The cycling T cell population is short lived, and the depleted memory compartment fuels the generation of new effector T cells. A catalyst for these phenomena is the increased responses to the cytokine IL-21, a mediator that regulates T cell turnover. We conclude that poor T cell survival and lymphopenia precipitate autoimmune disease.

Original languageEnglish (US)
Pages (from-to)265-277
Number of pages13
JournalCell
Volume117
Issue number2
DOIs
StatePublished - Apr 16 2004

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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