Lysis of CD4 + lymphocytes by non‐HLA‐restricted cytotoxic T lymphoe from HIV‐infected individuals

SUMMARY Individuals infected with HIV have elevated numbers of total and activated CD8 + lymphocytes in peripheral blood. CD8 + lymphocytes from HIV‐infected individuals have been shown to mediate non‐human histocompatibility‐linked antigen (HLA)‐restricted suppression of viral replication, HLA‐restricted killing of cells expressing HIV antigens, and killing of uninfected lymphocytes. We studied CD8 ( T lymphocytes that lysed autologous CD4+ lymphocytes, hetcrologous CD4 1 lymphocytes from HIV‐infected individuals and uninfected CD4 + lymphocytes. Killing in all cases required T cell receptor (TCR)‐mediated recognition or triggering. However, these CD8 cytotoxic T lymphocytes (CTL) killed HLA class I mismatched CD4* lymphocytes and CD4 4 lymphocytes treated with a MoAb against HLA‐A, B and C antigens (PA2.6) which blocks HLA class I‐restricted killing. HLA class H‐negativc CD4* T lymphoma cells (CEM.NK R ) were also killed by anti‐CD3 inhibited CTL. Stimulation of peripheral blood lymphocytes (PBL) from HIV‐infected individuals, but not uninfected controls, with concanavalin A (Con A) and IL‐2, induced non‐HLA‐restricted TCR aft 1 , CD8 f CTL which lysed CD4 + lymphocytes. Activation ofCD4’lymphocytes increased their susceptibility to CD8 f CTL‐mediated lysis. In HIV infection, a population of non‐HLA‐restricted CTL which lyse activated CD4 + lymphocytes is expanded. The expansion of CTL with unusual characteristics is interesting, because the stimulus for this expansion is unknown. CTL which recognize activated CD4 + cells could play a role in immune regulation and the pathogenesis of A IDS.