EXPRESSION OF HLA CLASS I-SPECIFIC INHIBITORY NATURAL-KILLER-CELL RECEPTORS IN HIV-SPECIFIC CYTOLYTIC T-LYMPHOCYTES - IMPAIRMENT OF SPECIFIC CYTOLYTIC FUNCTIONS

Human T lymphocytes have been shown to express inhibitory natural kill er cell receptors (NKR), which can down-regulate T cell antigen recept or-mediated T cell function, including cytolytic activity, In the pres ent study, we demonstrate that CD3+NKR+ cells can be identified in HIV -infected patients, HIV-specific cytolytic activity was analyzed in fi ve patients in whom autologous lymphoblastoid B cell lines could be de rived as a source of autologous target cells, Phytohemagglutinin-activ ated T cell populations that had been cultured in interleukin 2 displa yed HIV-specific cytotoxic T lymphocyte (CTL) activity against HIV env , gag, pol, and nef in 3 of 5 patients, Addition of anti-NKR mAb of Ig M isotype could increase the specific CTL activity, Moreover, in one a dditional patient, HIV-specific CTL activity was undetectable; however , after addition of anti-NKR mAb such CTL activity appeared ne novo. S imilar results were obtained by analysis of CD3+NKR+ clones derived fr om two patients, These data provide direct evidence that CD3+NKR+ cell s may include antigen (HIV)-specific CTLs and that mAb-mediated maskin g of inhibitory NKR may revert the down-regulation of CTL function.