Dys-regulation of effector CD4+ T cell function by the V3 domain of the HIV-1 gp120 during antigen presentation.

It was recently demonstrated that the semiconserved domain of the V3 region of the HIV-1 surface glycoprotein gp120 can induce an activation-apoptosis phenomenon to memory CD4+ cells from healthy individuals. Studying the effects of V3 on the interaction of antigen presentation between monocyte-derived macrophages and resting memory CD4+ T cells, we observed that V3 affects both cell populations. Macrophages exposed to composite liposomes containing V3 on the surface and tetanus toxoid (TT) as the recall antigen entrapped in the aqueous phase (lipoV3/TT liposomes) were able to activate CD4+ T cells during primary stimulation, but not after restimulation nine days later. Unstimulated macrophages or macrophages exposed to soluble TT responded to second stimuli, lipoV3/TT liposomes, and soluble TT in activating CD4+ T cells. Soluble TT-activated CD4+ T cells could be restimulated by soluble TT but not by lipoV3/TT liposomes, whereas lipoV3/TT liposome-activated CD4+ T cells became unresponsive to a second stimulus. These results show that resting memory CD4+ cells activated by macrophages presenting the recall antigen together with V3 become unresponsive to restimulation.