| Publication Abstract Display | | Type: Published Abstract | | Title: Enhancement of HIV specific T-cell responses by dendritic cell presentation. | | Authors: Schrier R, Cauvi G, Vanitha JD, Sanchez-Schmitz G, Higbee R, Torbett B | | Year: 2009 | | Publication: International Society for Cellular Therapy 15th Annual Meeting | | Volume: May 3-6 Issue: Pages: | | Abstract:Therapeutic immunization with HIV antigens has yet to be successful. This has inspired alternative approaches to enhance HIV specific immune responses in infected individuals. One approach is the use of antigen pulsed dendritic cells. In Vitro protocols for DC maturation have utilized cytokines GMCSF, IL-4, TNF, etc, to generate cytokine activated dendritic cells (CyDCs). In Vivo it is thought that monocyte migration through capillaries initiates differentiation into dendritic cells. In our In Vitro model, human monocytes migrated through umbilical vein derived vascular endothelial cells, differentiating into dendritic cells that we term: vaccination site dendritic cells (VSDCs). To determine the relative potency of CyDCs and VSDCs to present of HIV antigens, we evaluated the immune response profiles of 16 HIV infected subjects on ART, using HIV p24 protein and inactivated HIV with CMV pp65 protein and inactivated CMV as controls. Despite a relatively immature phenotype, VSDC from HIV-infected subjects, pulsed with HIV, elicited stronger CD4 and CD8 T-cell proliferation and IFNg expression at 6 days and at 24 hours, respectively, compared to pulsed CyDCs or the same antigens in soluble form. Single cell proliferation and cytokine analysis indicated that 40% of proliferating T-cells also expressed IFNg, while all IFNg+ cells also proliferated. Phenotypic analyses revealed that the proliferating cells from VSDC-mediated activation were primarily CD4+CD8-, secondarily CD4+CD8+, and a minor fraction were CD4-CD8+. In contrast, a higher proportion of CMV responding T-cells were CD4-CD8+. HIV and CMV pulsed VSDCs also induced CD107a expression, and most CD107a+ T-cells were CD4+. The presence of CD4 on potential CTLs suggests that they may be more receptive to HIV infection that previously appreciated. Our studies suggest that VSDCs more readily activate memory responses to HIV antigens than CyDCs and underscores the significance of a more physiological DC maturation process for initiating optimal immune responses. |
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