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