CD8+ cytotoxic T lymphocytes [CTLs] can provide resistance to tumors and infectious agents. Vaccines and immunotherapies that enhance CD8+ CTL responses therefore are critically needed. An effective way to induce CTLs is to present antigens on dendritic cells, """"""""nature's adjuvant"""""""". These are specialized antigen presenting cells for the initiation of many T cell dependent immune responses. Our laboratory has shown that human dendritic cells elicit strong MHC class I-restricted, anti-viral CD8+ CTLs from resting blood T cells in culture. We have now developed a methodology to obtain potent dendritic cells in large numbers. The goal of our clinical studies is to generate dendritic cells ex vivo from blood precursors, pulse the cells with antigens, and then test their capacity to boost T cell responses upon reinfusion into the original blood donor. We will first study immunization to model antigens in normal healthy individuals and then pursue CTL responses in HIV-1 infected individuals. The information gained will help develop the use of dendritic cells for purposes of vaccination and immunotherapy, and will provide the fundamentals for generating and studying CTL responses in vivo to other relevant viral and tumor antigens.
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