Dendritic cell-based vaccination to prevent opportunistic fungal infections

November 14, 2001

Because HIV depletes the population of CD4+ T cells, AIDS patients and others with immunosuppressive conditions are in a poor position to mount a protective response to vaccines. The absence of T cell help is particularly troublesome because of the opportunistic infections that are common among these patients. Noting that CD4+ cell-independent immunization would be useful to protect immunosuppressed people from infection by the fungus Pneumocystis carinii, Zheng et al. have tested a strategy that was recently developed to induce mucosal antibodies against a bacterial pathogen. This approach relies on dendritic cells (DC), which normally express the receptor CD40 and can be activated by the T cell?borne CD40 ligand, CD40L. Transfecting DC with the CD40L circumvents this step, allowing the DC to activate antigen-specific B cells directly. Zheng et al. generated mouse DC, transfected them with CD40L, and ?pulsed? them in vitro with Pneumocystis carinii, allowing them to display the pathogen?s peptides on their surface. As anticipated, the resulting DC conferred significant and apparently lasting protection against Pneumocystis pneumonia on mice, even though the host animals lacked endogenous CD4+ T cells. If DC from HIV infected individuals are capable of activating human B cells in this way, such an approach could provide an important adjunct to the standard antiretroviral therapies.
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