The role of HIV- and SIV-specific CD8+ T cells in the establishment of persistent HIV and SIV infections.

Abstract

CD8+ T cells are important in controlling viral infections. Although the appearance of HIV-specific CD8+T cells initially correlates with reduced viral load during HIV infection, for unknown reasons HIV is never fully cleared from the body. My central hypothesis is that B cell follicles are sites in which virus-producing cells are protected from virus-specific CD8+T cells. During the chronic stages of infection the majority of HIV-producing cells accumulate in B cell follicles. The localization and abundance of HIV-specific CD8+T cells relative to B cell follicles is not known. For these studies I determined the spatial localization of HIV and SIV-specific CD8+T cells relative to B cell follicles in lymph nodes from HIV-infected humans and SIV-infected rhesus macaques, using immunohistochemistry, in situ tetramer staining, confocal microscopy, and quantitative image analysis. My findings show that most HIV-specific CD8+T cells were concentrated in T cell zones and were largely excluded from areas within B cell follicles where HIV is concentrated. Because many similarities exist between HIV infection in humans and SIV infection in macaques, and SIV model systems are essential tools to understanding HIV/SIV infections and for the development of HIV vaccines, we set out to determine whether the exclusion of virus-specific CD8+T cells from B cell follicles also occurs in the SIV/rhesus macaque model of HIV infection. I found in a small cohort of animals that during the early and late stages of SIV infection, SIV-specific CD8+ T cells were concentrated in T cell zones of lymph nodes, and that within B cell follicles, concentrations of SIV-specific CD8+T cells were significantly lower than in T cell zones. Most B cell follicles showed an absolute exclusion of SIV-specific T cells from more than half of the B cell follicle area where SIV concentrates. These data support the hypothesis that B cell follicles are an immune privileged site in which HIV/SIV-producing cells are protected from HIV/SIV-specific CD8+T cells. These data have important implications for the development of a successful HIV vaccine and treatments to eradicate HIV.