ABROGATION OF IN-VITRO SUPPRESSION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-I (HIV-1) REPLICATION MEDIATED BY CD8(-LYMPHOCYTES OF ASYMPTOMATIC HIV-1 CARRIERS BY STAPHYLOCOCCAL-ENTEROTOXIN-B AND PHORBOL ESTERS THROUGH INDUCTION OF TUMOR-NECROSIS-FACTOR-ALPHA() T)

CD8(+) T lymphocytes of asymptomatic human immunodeficiency virus type 1 (HIV-1) carriers (AC) suppress HIV-1 replication in vitro, Failure of host defense mechanisms and increased virus proliferation are assoc iated with disease progression, The exact mechanisms inducing these ch anges at the advanced stage of the disease are still obscure. In this study, we searched for experimental conditions favoring the abrogation of the suppression of viral replication in peripheral blood mononucle ar cells (PBMC) of AC by' using various pharmacological and biological probes modifying cell activation. Among such agents, staphylococcal e nterotosin B (SEB) and phorbol 12-myristate 13-acetate (PMA) markedly increased otherwise low levels of HIV-1 replication in cultures of phy tohemagglutinin-stimulated AC PBMC following in vitro HIV-1 LAI infect ion, A similar but less pronounced virus induction was also observed i n macrophage-tropic HIV-1. Individual pretreatment of CD4(+) and CD8() PBMC fractions with these agents caused a reduction in CD8(+) cell p roliferation and enhanced HIV-1 replication in CD4(+) cells, SEB- and PMA-mediated augmentation of HIV-1 replication in AC PBMC was signific antly blocked by neutralizing antibody to tumor necrosis factor-alpha (TNF-alpha), although recombinant TNF-alpha alone failed to reproduce the effects of SEE or PMA. Our results suggest that the induction of T NF-alpha may be one of the mechanisms that overcomes the CD8(+)-induce d suppression of HIV-1 replication in AC and that it may induce HIV-1 replication.