CD8(+) cell lines isolated from HIV-1-infected children have potent soluble HIV-1 inhibitory activity that differs from beta-chemokines

CD8(+) cells from human immunodeficiency virus type 1 (HIV-1) infected indi viduals have been shown to suppress HIV-1 replication both through a major histocompatibility complex (MHC)-restricted cytolytic pathway as well as th rough a noncytolytic pathway mediated through soluble factors. To character ize this soluble activity and its potential role in disease progression fur ther, we studied the HIV-1 inhibition by supernatants derived from herpesvi rus saimiri-transformed CD8(+) cells isolated from infected children. Three of the six CD8(+) cell lines derived had a phenotype consistent with an un usual natural killer (NK) cells phenotype with low CD3, high CD56, and low CD16. Supernatants from some of the cell lines derived from children with r apid progression as well as long-term nonprogressors exhibited broad HIV-1- inhibitory activity in primary CD4(+) cells as well as in primary macrophag es. In contrast to a cocktail of beta -chemokines, the supernatants inhibit ed T-tropic as well as M-tropic viruses, efficiently inhibited infection in primary macrophages, and inhibited HIV-1 activation in the chronically inf ected U1 cell line. The HIV-1-inhibitory activity was heat stable and activ e over a broad pH range. Fractionation of the supernatant by size and ion e xchange chromatography demonstrated activity in the complete absence of RAN TES as well as interferons-alpha, beta, and gamma and in a size range of le ss than 10 kD and greater than 3 kD. CD8(+) cell supernatants contain addit ional unidentified factors that have anti-HIV activity to account for this broad phenomenon.