LIGATION OF EITHER CD2 OR CD28 RESCUES CD4(-CELLS FROM HIV-GP120-INDUCED APOPTOSIS() T)

Temporal or quantitative imbalance in signals delivered to T cells via T cell antigen receptor (TCR), the CD4 co-receptor, and accessory mol ecules can lead to anergy, apoptosis, or both. This has been observed following ligation of CD4 by HIV gp120 prior to TCR occupancy. The abi lity of molecules such as CD2 and CD28, interacting with their ligands LFA-3 and B7, to provide signals that protect T cells from the induct ion of anergy, has been reported. Here, we demonstrate that ligation o f CD2 and CD28 in conjunction with TCR occupancy rescue T cells that h ave been programmed for apoptotic death by prior CD4 ligation to gp120 . This appears to be the result of augmented interleukin-2 and interle ukin-4 release by the T cells following these molecular interactions. In conclusion, our results suggest that an impairment of antigen-prese nting accessory cell functions could favor gp120-mediated apoptosis in HIV-uninfected cells.