Studies by a variety of investigators, including ourselves, demonstrate that dendritic cells (DC) are extremely potent antigen presenting cells. When pulsed with protein antigens these cells, but not monocytes or B cells, induce primary antigen specific T cell responses both in vitro and in vivo in experimental animals. We have developed methods for obtaining enriched populations of DC from human peripheral blood and we have demonstrated that these cells, when pulsed with protein antigens or synthetic peptides, can sensitize naive T cells to these antigens, enabling the generation of antigen specific (including HIV specific) cytolytic T lymphocytes (CTL), in vitro. Most recently, we have demonstrated in humans that intravenous infusion of antigen pulsed DC can boost antigen specific T cell responses and is well tolerated. Taken together these observations suggest that infusion of HIV antigen pulsed DC may provide enhanced immunity to HIV, and we propose to evaluate this possibility in HIV infected patients. Specifically, we will isolate DC from health, uninfected donors, pulse these cells with HIV gp160 and infuse the pulsed cells monthly for 6 months into HLA identical, HIV infected siblings. In addition, we will work closely with the other scientists in this SPIRAT to generate HIV specific CD8+ and CD4+ CTL from uninfected sibling donors for purposes of adoptive immunotherapy. The HIV infected recipients of antigen pulsed DC and antigen specific CTL will be carefully monitored for changes in viral load and clinical status as well as the possible emergence of viral escape mutants.
