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. Pathogenic HIV and SIV infections of humans and Rhesus Macaques (RMs) result in progressive CD4+ T cell depletion and AIDS. In contrast, non-progressive SIV infection of sooty mangabeys (SMs) is characterized by preservation of CD4+ T cell counts. The mechanisms responsible for the differential ability to maintain CD4+ T cell homeostasis in SMs versus RMs are currently unknown. Scope of this recently awarded work is to elucidate the cellular and molecular basis for this divergent phenotype.
Specific aims i nclude the identification of species-specific features of CD4+ T cell reconstitution following antibody-mediated depletion of CD4 lymphocytes in vivo, and the definition of homeostatic regulation of a number of CD4+ T cell subsets that play a crucial role in the context of HIV/SIV infection, such as central memory, Th17, IL-21 producing cells. The project was funded in September 2010, and we are currently in the planning phase of the complex in vivo experiments included in Aim 1, in which 6 healthy RM will be treated with an anti-CD4 monoclonal antibody. We recently identified the 6 animals that have been already under quarantine and now assigned to the study. As such, we will soon start the proposed treatment aimed at depleting their CD4+ cells and then at investigating longitudinally the phenotypical, functional, and molecular profile of CD4+ T cells that proliferate in response to this depletion.
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