IDENTIFICATION OF MULTIPLE AND DISTINCT CD8(-CELL SUPPRESSOR ACTIVITIES - DICHOTOMY BETWEEN INFECTED AND UNINFECTED INDIVIDUALS, EVOLUTION WITH PROGRESSION OF DISEASE, AND SENSITIVITY TO GAMMA() T)

Using an in vitro model system that reflects the cellular interactions occurring in the microenvironment of lymphoid organs (i.e., the inter action between dendritic cells (DC) and CD4(+) T lymphocytes), the abi lity of CD8(+) T cells to inhibit HIV replication was investigated. DC , the most potent APC in the paracortical region of lymphoid organs, w ere cocultured with autologous, unstimulated CD4(+) T cells resulting in viral replication in the absence of exogenous stimulation. Using tw o variations of DC cocultures, one an acute infection system and the o ther an endogenous infection system, two sets of activities were ident ified, One activity was expressed in both HIV-infected and -uninfected individuals, and a second was found only in HIV-infected individuals. These activities can be differentiated further by their evolution or lack thereof with disease progression in infected individuals and thei r sensitivity to gamma irradiation. Furthermore, the results indicate that CD8(+) T cell modulation of HIV replication in CD4(+) T cells is a multifactorial phenomenon involving both inhibitory and stimulatory effects on HIV replication.