CD4-mediated functional activation of human CD4+CD25+ regulatory T cells

Eur J Immunol. 2007 May;37(5):1217-23. doi: 10.1002/eji.200636480.


Naturally occurring CD4(+)CD25(+)FoxP3(+) regulatory T cells (CD25(+) Tregs) constitute a specialized population of T cells that is essential for the maintenance of peripheral self-tolerance. The immune regulatory function of CD25(+) Tregs depends upon their activation. We found that anti-CD4 antibodies activate the suppressive function of human CD25(+) Tregs in a dose-dependent manner. We demonstrate that CD4-activated CD25(+) Tregs suppress the proliferation of CD4(+) and CD8(+) T cells, their IL-2 and IFN-gamma production as well as the capacity of CD8(+) T cells to re-express CD25. By contrast, anti-CD4 stimulation did not induce suppressive activity in conventional CD4(+) T cells. These results identify CD4 as a trigger for the suppressive function of CD25(+) Tregs and suggest a possible CD4-mediated exploitation of these cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / immunology
  • CD4 Antigens / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Coculture Techniques
  • Flow Cytometry
  • Humans
  • Immune Tolerance*
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Lymphocyte Activation / immunology*
  • T-Lymphocytes, Regulatory / immunology*


  • Antibodies, Monoclonal
  • CD4 Antigens
  • Interleukin-2 Receptor alpha Subunit