Objective:Determine whether natural killer (NK) cells are capable of killing HIV-infected autologous primary T-cell blasts.Design:The ability of NK cells to kill HIV-infected primary T-cell blasts, whose cell surface major histocompatibility complex (MHC) class I molecules was decreased, was evaluated in a lytic assay.Methods:Phytohemagglutinin-treated CD4+ T cells were infectedin vitrowith HIV-1. Infected cells were separated from uninfected cells by removal of CD4+ T cells. The NK cells were isolated from peripheral blood mononuclear cells (PBMC) of the same donor as the CD4+ T cells by immunomagnetic bead separation. The NK cells isolated from PBMC were then used as effector cells and the HIV-infected T-cell blasts were used as target cells in a lytic assay.Results:It was demonstrated that HIV infection of primary CD4+ T cells results in a 61–68% reduction in surface expression of MHC class I molecules. Despite the decreased MHC class I expression the NK cells were incapable of lysing autologous HIV-infected T-cell blasts, yet were effective in the lysis of the NK cell sensitive cell line, K562. The inability of NK cells to lyse HIV-infected T-cell blasts is not dependent on the strain of HIV used to infected the CD4+ T cellConclusion:These studies indicate that despite drastic decreases in MHC class I molecule expression, HIV-infected T-cell blasts can evade destruction by autologous NK cells.