TH17 CELLS IN AIDS PATHOGENESIS AND HIV VACCINES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Th17 cells are preferentially depleted in pathogenic HIV/SIV infections of humans and rhesus macaques (RM), but not in nonpathogenic SIV infection of sooty mangabeys (SM). The overall aim of this project, funded 16 months ago, is to elucidate the mechanisms regulating Th17 homeostasis in progressive and nonprogressive lentiviral infections. In this period, we first expanded upon the original observation that mucosal Th17 are depleted in HIV-infected humans by increasing the numbers of enrolled subjects. This part of the study is now completed, with our population including 28 HIV-infected individuals and 11 controls. The higher numbers of individuals allowed us to perform a number of correlations. Interestingly, we found that in HIV infection the severity of Th17 depletion correlates with levels of immune activation, but not with viral load. These data have been included in a published manuscript (see publication). In addition, we started the study detailed in sub-Aim #1c in which six RM have been SIV infected and will be treated with antiretroviral therapy (ART) in the chronic infection. This study will provide key information on Th17 reconstitution when virus replication is suppressed, and on the effect on Th17 by the viral rebound that will follow ART interruption. Additionally, we successfully identified Th17 precursors and cells producing Th17-differentiating cytokine, such as IL-21, and the analyses of the levels of these cells in SIV infected and uninfected nonhuman primates are in progress.