GENERATION OF CD8 SUPPRESSOR FACTOR AND BETA-CHEMOKINE, INDUCED BY XENOGENEIC IMMUNIZATION, IN THE PREVENTION OF SIMIAN IMMUNODEFICIENCY VIRUS-INFECTION IN MACAQUES

Previous xenogeneic immunization experiments in rhesus macaques with s imian immunodeficiency virus (SIV) grown in human CD4(+) T cells consi stently elicited protection from challenge with live SIV, However, the mechanism of protection has not been established. We present evidence that xenogeneic immunization induced significant CD8 suppressor facto r, RANTES (regulated upon activation, normal T cell expressed and secr eted), macrophage inflammatory protein (MIP) 1 alpha, and MIP-1 beta ( P < 0.001 - P < 0.02), The concentrations of these increased significa ntly in protected as compared with infected macaques (P < 0.001). Xeno geneic stimulation in vitro also up-regulated CD8 suppressor factors ( SF; P < 0.001) and the beta chemokines which were neutralized by antib odies to the 3 beta chemokines. Recombinant human RANTES, MIP-1 alpha and MIP-1 beta which bind to simian CCR5, suppressed SIV replication i n a dose-dependent manner, with RANTES being more effective than the o ther two chemokines. The results suggest that immunization with SIV gr own in human CD4(+) T cells induces CDS-suppressor factor, RANTES, MIP -1 alpha and MIP-1 beta which may block CCR5 receptors and prevent the virus from binding and fusion to CD4(+) cells.