Homeostatic Expansion of T Cells During Immune Insufficiency Generates Autoimmunity

Cell. 2004 Apr 16;117(2):265-77. doi: 10.1016/s0092-8674(04)00335-6.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoimmunity / immunology*
  • Cell Count
  • Cell Division / immunology
  • Cell Survival / immunology*
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / physiopathology
  • Disease Models, Animal
  • Homeostasis / immunology
  • Interleukin-21 Receptor alpha Subunit
  • Interleukins / immunology*
  • Lymphopenia / immunology*
  • Lymphopenia / physiopathology
  • Mice
  • Mice, Inbred NOD
  • Receptors, Interleukin / immunology
  • Receptors, Interleukin-21
  • T-Lymphocytes / immunology*

Substances

  • IL21R protein, human
  • Il21r protein, mouse
  • Interleukin-21 Receptor alpha Subunit
  • Interleukins
  • Receptors, Interleukin
  • Receptors, Interleukin-21
  • interleukin-21