This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Throughout the period of this project, we have continued to examine the mechanisms by which CD4+ T cells are eliminated in SIV infection, examine the tissues involved in viral replication, and to measure the rate at which CD4+ T cells turn over in sequestered tissues such as the intestine, bone marrow, spleen, liver, nervous system, and lymph nodes. Using tissues from these projects, our collaborators have shown that the intestinal nervous system is affected in early SIV infection (Orandle et al). This year, our lab has focused on examining viral infected cells in tissues using immunohistochemistry and RT-PCR on sorted cell subsets to demonstrate that memory CD4+ T Cells are selectively infected and eliminated early in SIV infection. One manuscript has been submitted demonstrating the loss of CD4+ T cells is independent of CD8+ T cell mediated killing and another is being prepared. We have also found that percentages of proliferating CD4+ T cells are increased in virtually all tissues of SIV-infected adults and are currently focusing on quantitative assessments of T cell turnover in the bone marrow and liver, to distinguish de novo T cell generation from tissue expansion of pre-existing memory T cell subsets.
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