HERPESVIRUS SAIMIRI TRANSFORMATION OF HIV TYPE-1 SUPPRESSIVE CD8-INFECTED ASYMPTOMATIC INDIVIDUAL( LYMPHOCYTES FROM AN HIV TYPE 1)

CD8(+) T lymphocytes from HIV+ individuals can potently suppress HIV-1 replication in a noncytolytic manner. This suppression appears to be multifactorial and the molecules contributing have not been fully eluc idated. As an approach to this question we used herpesvirus saimiri (H VS) to transform CD8(+) T lymphocytes from an HIV+ asymptomatic donor to a continuously growing, activation-independent, IL-2-dependent phen otype. The transformed cell population, termed CD8(HVS), had an activa ted phenotype, contained HVS sequences, did not shed infectious HVS vi rus, and was polyclonal. The CD8(HVS) cells, despite the absence of de tectable CTL activity, potently suppressed HIV-1 production by both au tologous and heterologous CD4(+) cells from infected donors. The CD8(H VS) cells in coculture also suppressed virus production from PBMCs acu tely infected with syncytium-inducing (SI) strains or NSI primary isol ates of HIV-1. The supernatants from the CD8(HVS) cells and their conc entrates derived from these supernatants were suppressive to NSI prima ry isolates of HIV-1 but not to SI strains. Fractionation of these con centrates showed that the suppressive activity was associated with low molecular mass (6500- to 19,300-Da) protein species. Western blotting and ELISA indicated that the CC chemokines MIP-1 alpha, MIP-1 beta, a nd RANTES were present in these fractions. Antibody-blocking studies w ith antibodies to the CC chemokines indicated that a significant porti on of the soluble HIV-suppressive activity was due to these molecules. However, these experiments also suggested the inhibitory activity of the CD8(HVS) cells in coculture is not due exclusively to the CC chemo kines. The HVS-transformed cells provide a useful tool for the study o f noncytolytic CD8(+) T lymphocyte-mediated suppression of HIV-1.