DUAL FUNCTION OF A HUMAN-IMMUNODEFICIENCY-VIRUS (HIV)-SPECIFIC CYTOTOXIC T-LYMPHOCYTE CLONE - INHIBITION OF HIV REPLICATION BY NONCYTOLYTICMECHANISMS AND LYSIS OF HIV-INFECTED CD4+ CELLS

CD8+ T cells may play a beneficial role in human immunodeficiency viru s (HIV)-infected patients by two mechanisms: HIV-specific cytotoxic ac tivity and secretion of a soluble mediator(s) that inhibits HIV replic ation in vitro. Here we characterized both activities mediated by an H IV p24(gag)-specific cytotoxic T lymphocyte (CTL) CD8+ clone derived f rom an HIV-infected patient. When the CTL clone was mixed with HIV-inf ected autologous CD4+ T cells, viral replication was suppressed. This viral inhibition was observed in heterologous CD4+ T cells and when CD 8+ and CD4+ populations were separated by a semipermeable membrane, de monstrating the involvement of a diffusible factor(s), The lysis of au tologous HIV-infected T cells was also detected. However, HIV suppress ion was more efficient when CD4+ and CD8+ T cells shared major histoco mpatibility complex alleles and were in direct contact. Thus, one and the same CD8+ T cell population can mediate both lysis of HIV-infected targets and nonlytic suppression of HIV replication. These results un derline the multiple roles of CD8+ T lymphocytes in the suppression of HIV-infected cells. (C) 1996 Academic Press, Inc.