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. This project investigates the potential for cytokines promoting cell mediated immune responses for restoring/augmenting antiviral immune responses following SIV infection by administration of IL-12 alone or in combination with IL-2 or Il-15 and a structured antiviral chemotherapy interruption protocol using PMPA. The past year has been devoted primarily to the monitoring of the rhesus infected with SIVmac251 and treated with STI and IL-12. Surviving monkeys with variable levels of immune mediated control of the SIV viremia have been subjected to chronic administration of IL-15 followed by IL-7 to document the effect of these T cell directed cytokines on the viral loads and antiviral immune responses in vivo. In addition, parallel studies were initiated in sooty mangabeys in attempt to delineate T cell dysfunction in the pathogenic rhesus vs non pathogenic mangabey monkey. The role of regulatory T cells was investigated longitudinally in both models as well as the potential role of PD-1 expression on CD4 and CD8+ T cells. In addition, a preliminary evaluation of the in vivo administration of inhibitors of potassium channels specific for central memory and effector memory T cells was performed in conjunction with an immunization with influenza. The project is near its completion and the final four animals are being observed for longterm effects of the therapy.
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