CD4 + CD25 + Immunoregulatory T Cells Suppress Polyclonal T Cell Activation In Vitro by Inhibiting Interleukin 2 Production

  • Thornton A
  • Shevach E
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Abstract

Peripheral tolerance may be maintained by a population of regulatory/suppressor T cells that prevent the activation of autoreactive T cells recognizing tissue-specific antigens. We have pre- viously shown that CD4  CD25  T cells represent a unique population of suppressor T cells that can prevent both the initiation of organ-specific autoimmune disease after day 3 thymec- tomy and the effector function of cloned autoantigen-specific CD4  T cells. To analyze the mechanism of action of these cells, we established an in vitro model system that mimics the function of these cells in vivo. Purified CD4  CD25  cells failed to proliferate after stimulation with interleukin (IL)-2 alone or stimulation through the T cell receptor (TCR). When cocul- tured with CD4  CD25  cells, the CD4  CD25  cells markedly suppressed proliferation by specifically inhibiting the production of IL-2. The inhibition was not cytokine mediated, was dependent on cell contact between the regulatory cells and the responders, and required activa- tion of the suppressors via the TCR. Inhibition could be overcome by the addition to the cul- tures of IL-2 or anti-CD28, suggesting that the CD4  CD25  cells may function by blocking the delivery of a costimulatory signal. Induction of CD25 expression on CD25  T cells in vitro or in vivo did not result in the generation of suppressor activity. Collectively, these data sup- port the concept that the CD4  CD25  T cells in normal mice may represent a distinct lineage of “professional” suppressor cells.

Author-supplied keywords

  • autoimmune disease
  • cd25
  • chain
  • interleukin 2
  • interleukin 2 receptor
  • self-tolerance
  • suppressor t cells

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Authors

  • Angela M Thornton

  • Ethan M Shevach

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