The infiltration kinetics of simian immunodeficiency virus-specific T cells drawn to sites of high antigenic stimulation determines local in vivo viral escape

Despite vigorous cell-mediated immune responses to human and simian immunod eficiency viruses (HIV/SIV) the immune system is unable to clear latently i nfected resting T cells. These infected cells are reactivated by antigenic stimulation, leading to viral replication. By using the SIV/macaque model o f HIV pathogenesis, the dynamics of T cell infiltration into delayed type h ypersensitivity sites specific for the purified protein derivative of bacil lus Calmette-Guerin have been studied. Early viral mRNA synthesis coincided with the infiltration of antigen-specific T cells. When the infiltration o f anti-SIV-specific T cells was rapid compared with the kinetics of viral a ssembly, the sites were sterilized before the transition to late viral mRNA synthesis occurred. When their infiltration was slow, ephemeral foci of re plication were identified. These findings were paralleled by plasma viremia ; low viremia coincided with rapid sterilization of the delayed type hypers ensitivity sites, whereas high load was found in association with local rep lication and delayed sterilization. These data suggest that although effect ive local control of SIV is possible once antiviral T lymphocytes have arri ved on site, the slower deployment of these T cells may allow the virus to escape and thus to reseed the pool of memory T cells.