DECREASED ABILITY OF HIV-1 TAT PROTEIN-TREATED ACCESSORY CELLS TO ORGANIZE CELLULAR CLUSTERS IS ASSOCIATED WITH PARTIAL ACTIVATION OF T-CELLS

It has been shown in several animal models that HIV infection of acces sory cells (ACs) plays an important role in development of AIDS. Here, nit report that ACs treated with HIV-1 Tat protein (Tat-ACs) have a d ecreased ability to organize cellular aggregates as compared with untr eated ACs, resulting in incomplete activation of T cells in responses to anti-CD3 mAb or staphylococcal enterotoxin B stimulation. The T tel ls failed to up-regulate adhesion molecules CD11a and CD2 on the cell surface and had reduced proliferative responses, as determined by [H-3 ]thymidine incorporation, but they obtained lymphoblast-like morpholog y and expressed early activation antigens on the cell surface such as Fas acid CD69 and interleukin 2 receptor, at comparable levels as thos e T cells undergoing a maximal proliferation. These results suggest th at the Tat-AC-induced defect occurs in the late, rut not in the early, phases of T cell activation. Normal expression of cell surface Pas an tigen accompanied by defects in late activation thus may result in the susceptibility of these T cells to apoptosis. Our studies suggest tha t dysfunction, hyperactivation, and susceptibility to apoptosis, as ob served with T cells isolated from HIV-infected individuals, may be, at least in part, a consequence of abnormal functions of ACs.