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. T cells can produce multiple different cytokines and their co-expression profiles vary significantly depending on their maturation state. Many factors, including the persisting levels of antigen, can influence the maturation state of T cells and their cytokine co-expression profile. To determine the cytokine co-expression profile of CD4 and CD8 T cells from HIV-1 infected individuals and the influence of plasma viremia, we conducted a cross-sectional evaluation of HIV-specific T cells from 19 HAART na ve and 20 HAART recipients. These studies revealed that both CD4 and CD8 T cells in infected patients were defective in IL-2 production and that this defect could be partially rescued for CD4 T cells with time on antiretroviral drug treatment. CD4 T cells in infected patients are being further studied for their cytokine production patterns. Overall, the total HIV-specific CD4 response appears to be more polyfunctional, or capable of producing a variety of cytokines, in long term non-progressors than in untreated patients. Treatment with antiretroviral drugs partially restores the presence of polyfunctional T cells. Effort has also been placed on establishing GLP assays for T cell responses in ancillary assays on samples that will be generated during the phase 1a/1b trial of our clade B vaccine by the NIH HIV Vaccine Trials Network. The GLP assays to be conducted include thymidine proliferation assays, ELISPOT assays for IFN-? and IL-2 and intracellular cytokine staining for IFN-? and IL-2.
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