Abstract

The effect of extracellular HIV Nef ( exNef) protein on the induction of lytic activity and proliferation of CD8 +T lymphocytes from 18 donors was studied. At 10 ng/ml, exNef-induced a 2- to 8-fold enhancement of basal lytic activity in cells from all donors in an allogeneic induction assay, whereas it was ineffective at 100 ng/ml. The extent of enhancement was inversely correlated with the basal level of lytic activity without exNef. Only in combination with PHA did both exNef concentrations stimulate proliferation, and in a manner inversely related to the effect of PHA alone. Thus, concentrations of exNef commonly found in sera of HIV-infected patients were found to modulate the induction of lytic activity and proliferation of CD8 + T lymphocytes in vitro, to an extent strongly dependent on the quite variable responsiveness of each donor. These findings point to Nef as a potential agent for modulating CD8 + T cell function in pathogenesis and therapy.

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