CD8(-CELLS FROM HIV TYPE 1-SERONEGATIVE INDIVIDUALS SUPPRESS VIRUS-REPLICATION IN ACUTELY INFECTED-CELLS() T)

CD8(+) lymphocytes (CDS cells) have been shown to inhibit replication of the human immunodeficiency virus (HIV) in vitro when cocultured wit h HIV-infected CD4(+) lymphocytes (CD4 cells), This suppressive effect on HIV replication in experimentally infected CD4 cells has so far be en demonstrated only for CD8 cells from HIV-seropositive individuals. In the present study we have investigated if CD8 cells from HIV-negati ve individuals can also suppress HIV replication in experimentally inf ected CD4 cells. Positively selected CD4 cells were infected with phen otypically different primary isolates of HIV type 1 and 2 (HIV-1 and H IV-2). Graded numbers of CD8 cells were added to the infected cultures . The T cells were activated by antibodies directed against the CD3 mo lecule or the T cell receptor. Culture supernatants were harvested for HIV p24 quantitation and the CD8 suppression of HIV replication was c alculated by comparing p24 levels from parallel cultures in the presen ce or absence of CD8 cells from different donors. We show that CD8 cel ls from unexposed HIV-seronegative blood donors are able to control HI V-1 and HIV-2 replication in experimentally infected autologous CD4 ce lls, The antiviral activity of CD8 cells from an HIV-naive individual was reproducible over time and the suppressive effect was comparable t o that seen with CD8 cells from HIV-positive individuals. The infected cells were not eliminated from the cocultures, The suppressive effect of CD8 cells varied depending on the dose and biological phenotype of the virus used for infection. Thus, exposure to HIV in vivo is not a prerequisite for CD8 cells to exert a suppressive effect on HIV replic ation in acutely infected cells.