Natural killer cell-mediated lysis of T cell lines chronically infected with HIV-1

Abstract

SUMMARY The susceptibility of HIV-1-infected CD4+ T cell lines to natural killer(NK) cell-mediated lysis was examined. Non-adherent peripheral blood mononuclear cells (PBMC) of healthy adults lysed HUT cells chronically infected with the HJB or WMJI strains of HIV-1 to a significantly grater extent than uningected HUT cells. In contrast, Sup-T1 cells chronically infected with these two strains of HIV-1 were not lysed to a greater extent than uninfected Sup-T1 cells. Clone AI. 25-infected Sup. T1 (A1.25/Sup. T1), derived from HIB-infected Sup. T1 cells (HIB/Sup-T1), were susceptible to non-adherent PBMC-mediated lysis as were A1.25-infected HUT cells (A1.25/HUT). When non-adherent PBMC were depleted of CD16 (Leu-Hb) NK cells by treatment with and-Leu-Hb plus C lysis of HIV-1-infected HUT or Sup-T1 cells was reduced to low levels, indicating that the lysis was mediated by NK cells. Expression of HIV antigens on these target cells did not correlate with their susceptibility to NK cell-mediated lysis. Depletion of interferon-alpha (IFN-α) producing HLA-DR1 cells from non-adherent PBMC had no effect on the magnitude of NK cell-mediated lysis of HIB or WMJI-infected HUT cells. In contrast, lysis of A1.25/Sup-T1 or A1.25/HUT cells required the presence of HLA-DR1 cells. IFN-α production appeared to be required for NK cell-mediated lysis of A1.25/Sup-T1 or A1.25/HUT cells, while lysis of Hut cells infected with the WMJI ro HUB strains of HIV-1 was IFN-α independent. These results indicate considerable variability in the susceptibility of different HIV-1 infected T cell lines to NK cell-mediated lysis and suggest the existence of alternative mechanisms of activation of NK cells for lysis of HIV-1-infected T cell lines.