Human CD4+CD25+ regulatory cells have marked and sustained effects on CD8+ T cell activation

Eur J Immunol. 2003 Dec;33(12):3473-83. doi: 10.1002/eji.200323966.


Amongst the many types of regulatory cells that have been described during the past few years, the spontaneously occurring population that is characterized by co-expression of CD4 and CD25 appears to play a key role in the prevention of autoimmunity and the maintenance of transplantation tolerance. In this study we have examined the ability of CD4(+)CD25(+) T cells to regulate human CD8(+) T cells, and the behavior of CD8(+) T cells following activation in the presence of regulatory CD4(+)CD25(+) T cells. The experiments described here demonstrate that human CD4(+)CD25(+) T cells cause pronounced and sustained inhibition of CD8(+) T cell proliferation in response to polyclonal and allogeneic stimulation. The regulation of CD8(+) T cell activation was cell contact-dependent and included inhibition of perforin, granzyme B and IFN-gamma cytokine production at the transcriptional level and impaired cytotoxicity. The regulated CD8(+) T cell population showed sustained hyporesponsiveness and refractoriness to exogenous IL-2. These data provide insights into the short- and long-term effects of CD4(+)CD25(+) T cells on CD8(+) T cells that could be of considerable value in optimizing vaccination against tumor and viral antigens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / physiology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Communication
  • Cell Differentiation
  • Coculture Techniques
  • Cytokines / physiology
  • Humans
  • Lymphocyte Activation*
  • Receptors, Interleukin-2 / analysis*
  • T-Lymphocytes, Cytotoxic / physiology


  • Cytokines
  • Receptors, Interleukin-2