In vivo T-lymphocyte activation and transient reduction of viral replication in macaques infected with simian immunodeficiency virus

While it is well established that cellular activation can increase human im munodeficiency virus (HIV) replication in T lymphocytes, it is also clear t hat both activated CD8(+) and CD4(+) T lymphocytes mediate anti-MN activity . To assess the relative importance of these contrary effects on HIV replic ation in vivo, we evaluated the consequences of Mycobacterium bovis BCG and staphylococcal enterotoxin B (SEB) inoculation in vivo in rhesus monkeys c hronically infected with simian immunodeficiency virus of macaques (SIVmac) . BCG inoculation induced as much as a 2.5-log reduction of plasma and intr acellular SIV RNA in SIVmac-infected monkeys. This down-regulation of virus replication persisted as long as 4 weeks after BCG inoculation. Similarly, SEE injection resulted in up to a 3-log decrease in plasma and intracellul ar SIV RNA in SIVmac-infected macaques. Interestingly, the short-term reduc tion of viremia in these monkeys correlated with the peak in vivo productio n of SEB- and BCG-induced cytokine responses. However, no long-term clinica l benefit was observed in the SIVmac-infected macaques. These studies provi de in vivo evidence that potent T-cell stimulation driven by antigens other than the virus itself can, under some circumstances, mediate short-term re duction of viremia in AIDS virus-infected individuals.