Abstracts (complete list) - Wissenschaft Online

Christian Becker, Tobias Bopp, Jan Kubach, Franz-Josef Schneider, Edgar Schmitt,
Helmut Jonuleit
CD4-mediated, TCR-independent functional activation of
human CD4+CD25+ regulatory T cells
CD4 coreceptors exert complex regulatory effects on T cell activation and function. We
recently showed that engagement of CD4 by specific anti-CD4 antibodies induce
suppressive activity in human CD25+Foxp3+ regulatory T cells (Tregs). CD4 mediated
activation of Tregs acts independently of TCR stimulation but elicits comparable
suppressive activity resulting in efficient suppression of effector T cell proliferation and
cytokine production. Examination of the proximal CD4 signaling events in Tregs after
CD4 ligation shows phosphorylation of the zeta-associated protein-70 which relays
signals to downstream signaling components. Selective inhibition of lck activity during
anti-CD4 stimulation prevents induction of suppressive function in CD25+ Tregs. In
contrast to Tregs, CD4 ligation of CD4+CD25- T cells by anti-CD4 cross-linking does not
induce suppressive activity.
Here we show that the HIV-derived CD4 binding envelope glycoprotein gp120 is a
potent functional activator of human Tregs. Upon stimulation with gp120, Tregs
substantially increase production of cAMP, a second messenger previously shown to be
essentially involved in Treg-mediated suppression. These results demonstrate that
suppressive activity in human Tregs can be directly triggered by gp120, suggesting that
immune dysfunctions associated with HIV infection might in part result from CD4mediated
Treg activation by the virus.