Dendritic cells and immune-based therapies.

The dendritic cell (DC) lineage of white blood cells specializes in capturing antigens and stimulating T-dependent immunity. Because of their efficacy in inducing T cell responses in vivo without other adjuvants, DCs can be considered "nature's adjuvant." DCs are the least abundant of leukocytes, but methods for generating large numbers of DCs are being developed. Ex vivo, DCs develop from CD34+ progenitors cultured in the presence of a combination of granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha). This kind of work is stimulating interest in charging DCs with clinically relevant antigens and inducing active immunity in patients. Targeting antigens to DCs may become feasible also because of the identification of distinct antigen receptors such as DEC-205, a DECalectin with 10 contiguous, C-type lectin domains. DEC-205 can mediate adsorptive uptake and presentation via DCs. AIDS is another disease for which DCs should be considered in designing new therapies, since DCs can play a major role in promoting HIV-1 replication. Many HIV-1 isolates induce syncytia between DCs and CD4+ memory T cells. These syncytia in turn are the site for a productive infection with HIV-1, possibly because requisite transcription factors like NF-kappaB and Sp1 are separately provided by DCs and T cells, respectively. Further attention to the DC lineage should provide new avenues for manipulating the immune system in several clinical contexts.