6533b82bfe1ef96bd128e392

RESEARCH PRODUCT

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

Jürgen KnopChristian BeckerJan KubachJohn WijdenesHelmut Jonuleit

subject

ImmunologyInterleukin-2 Receptor alpha SubunitAntibodies MonoclonalFOXP3hemic and immune systemschemical and pharmacologic phenomenaCD8-Positive T-LymphocytesBiologyFlow CytometryLymphocyte ActivationT-Lymphocytes RegulatoryCoculture TechniquesImmune toleranceCell biologyInterleukin 21Immune systemCD4 AntigensImmunologyImmune ToleranceHumansImmunology and AllergyCytotoxic T cellIL-2 receptorCell activationCD8

description

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.

https://doi.org/10.1002/eji.200636480