Diminution of inducible lymphokine-activated killer cell activity in individuals with AIDS-related disorders

We have compared the relative ability of lymphokine-activated killer (LAK) cells derived from peripheral blood of HIV-seropositive people, AIDS subjects, and healthy controls, to lyse a panel of natural killer (NK)-sensitive and NK-resistant tumor and virally-infected targets. We have found that LAK cells derived from HIV-seropositive populations show a significant, albeit reduced, capacity to lyse U937, K562, and RAJI target cell lines, in comparison with similarly derived cells from healthy controls. The reductions in LAK activity in both HIV-seropositive asymptomatic and AIDS populations reflect a significant reduction in cytotoxic potential of individual LAK cells. The maximal LAK cytotoxic potentials of control, asymptomatic seropositive, and AIDS populations are comparable. LAK cells derived from HIV-seropositive populations show an enhanced capacity to lyse HIV-infected U937 targets relative to their uninfected counterparts. These enhancements in HIV-infected U937 versus U937 cytolysis arise from increases in the maximal cell-mediated cytolytic plateau. Depletion of NK (CD56+) lymphocytes from peripheral blood prior to LAK cell generation markedly diminishes subsequent specific and total inducible LAK activity. In some subjects, peripheral blood T-cell depletion prior to LAK cell generation results in LAK cells that are subsequently enriched for cytolytic activity, whereas in other subjects similar T-cell depletion impairs inducible LAK cell responses.