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. This project is aimed at immune reconstitution of SIV infected macaques comparing autologous CD4+ T cells collected prior to versus post SIV infection and expanded in vitro using anti-CD3/anti-CD28 coated immunobeads. As we gathered data during the reporting period, our aim was to evaluate the need for longevity of the adoptively transferred CD4+ T cells for antiviral control. This was achieved by transducing the adoptively transferred cells with a construct expressing the thymidine kinase gene in vivo. First, the data confirmed that success of the therapy was tied with the capacity to temporarily fully control viremia at the time of initiation of adoptive transfer of autologous CD4 T cells. Next, gancyclovir mediated elimination of adoptively transferred CD4+ T cell at six weeks following transfer showed delay in achieving antiviral control as well as incomplete control of viremia below the detection threshold of the assay. This data confirmed the finding that adoptively transferred CD4+ T cells are long-lived, re-circulate extensively post transfer and that their proliferation is directly proportional to the level of viremia in vivo.
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