This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The objective of this project is to examine T regulatory cells (Tregs) in Rhesus macaques (Rh) and African green monkeys (AGMs). Tregs, initially defined as CD4+CD25+, suppress T-cell activation and proliferation in vitro and in vivo in both mice and humans. As chronic immune activation and rapid turnover of T cells are hallmarks of pathogenic HIV/SIVmac infections in humans and Rh, these cells may play an important role in HIV/SIV pathogenesis. Our preliminary studies of the dynamics of CD4+CD25+ T cells in SIVmac-infected Rh showed a loss of this T cell subset that may explain the aberrant chronic T cell hyperactivation described in pathogenic infection. We also found an increase in the number of Tregs during very early stages of SIVagm infection and a better preservation of this T cell subset in chronically SIVagm-infected AGMs. The pattern of CD4+CD25+ T cell dynamics in SIVagm-infected AGMs corroborates the lack of immune activation and turnover during lentiviral infections in natural hosts of SIVs, which rarely develop AIDS. We therefore hypothesize that Tregs have a protective role in SIV infection. In order to clearly define the role of Tregs in pathogenic and non-pathogenic SIV infections, we designed experiments in this pilot study for normal, uninfected Rh and AGMs to confirm the existence of fully functional Tregs and to verify our ability to identify and manipulate this T cell subset. To date we identified fully functional Tregs in normal AGMs and Rh, able to inhibit T cell proliferation in vitro. We set up a real-time PCR assay for FOX-P3, the best marker for Tregs to date. We also tested four clones of FOX-P3 and we identified three that cross-react well with Rh PBMCs and two that show good cross-reactivity with AGMs PBMCs.
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