CD4-mediated functional activation of human CD4+CD25+ regulatory T cells.
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.
Becker
Christian
C
Department of Dermatology, Johannes Gutenberg-University, Mainz, Germany. christian.becker@hautklinik.klinik.uni-mainz.de
Kubach
Jan
J
Wijdenes
John
J
Knop
Jürgen
J
Jonuleit
Helmut
H
D000911:Antibodies, Monoclonal / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018920:Coculture Techniques; D005434:Flow Cytometry; D006801:Humans; D007108:Immune Tolerance; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit