CHANGES IN NATURAL IMMUNITY DURING THE COURSE OF HIV-1 INFECTION

The role of natural killer (NK) and lymphokine-activated killer (LAK) cell-mediated cytotoxicity in AIDS has yet to be established. The obje ctive of this study was to determine inducible LAK cell responses at d ifferent stages of HIV-1 infection, and specifically to establish the participation of CD8 lymphocytes in these responses. Peripheral blood lymphocytes (PBL) were isolated from healthy seronegative (CDC-0) subj ects and HIV-11 individuals who were clinically asymptomatic (Centre f or Disease Control group 2, CDC-2) or symptomatic (CDC-4) with regard to secondary opportunistic infection (01). LAK cells were generated up on incubation of PBL with IL-2 and their cytolysis of K562 and U-937 t argets was determined using chromium release assays. The role of CD8lymphocytes as progenitors and effectors of these LAK cell responses w as determined by immunomagnetic depletion of CD8+ cells from precursor PBL and LAK cells, respectively. LAK cell-mediated cytotoxicities in HIV-1-infected individuals were reduced compared with seronegative con trols without any corresponding changes in the relative proportions of CD56+ (NK) cells among groups. Depletions of CD8 + subsets from eithe r PBL or LAK cells dramatically reduced total LAK cytotoxic responses and LAK activities per unit CD56+ cell in the OI-/CDC-2 seropositive p opulation. No corresponding changes in LAK activities in seronegative control or HIV+/OI+/CDC-4 groups were observed. Levels of LAK activity against K562 targets in CDC-0/HIV- and CDC-4/HIV+ groups correlated w ith the percentage of CD56+ LAK cells; corresponding LAK activity in t he CDC-2/HIV+ group correlated with the percentage of both CD56+ and C D8+ subsets. These findings suggest that adaptive changes in non-MHC r estricted cytotoxic responses occur in HIV-1 individuals at early stag es post-HIV infection, before the onset of opportunistic infection.