CD4(+) T cell-independent vaccination against Pneumocystis carinii in mice

Host defenses are profoundly compromised in HIV-infected hosts due to progr essive depletion of CD4(+) T lymphocytes. Moreover, deficient CD4(+) T lymp hocytes impair vaccination approaches to prevent opportunistic infection. T herefore, we investigated a CD4(+) T cell-independent vaccine approach to a prototypic AIDS-defining infection, Pneumocystis carinii (PC) pneumonia. H ere, we demonstrate that bone marrow-derived dendritic cells (DCs) expressi ng the murine CD40 ligand, when pulsed ex vivo by PC antigen, elicited sign ificant titers of and-PC IgG in CD4-deficient mice. Vaccinated animals demo nstrated significant protection from PC infection, and this protection was the result of an effective humoral response, since adoptive transfer of CD4 -depleted splenocytes or serum conferred this protection to CD4-deficient m ice. Western blot analysis of PC antigen revealed that DC-vaccinated, CD4-d eficient mice predominantly reacted to a 55-kDa PC antigen. These studies s how promise for advances in CD4-independent vaccination against HIV-related pathogens.