DENDRITIC CELLS AND IMMUNE-BASED THERAPIES

The dendritic cell (DC) lineage of white blood cells specializes in ca pturing antigens and stimulating T-dependent immunity. Because of thei r efficacy in inducing T cell responses in vivo without other adjuvant s, DCs can be considered ''nature's adjuvant.'' DCs are the least abun dant of leukocytes, but methods for generating large numbers of DCs ar e being developed. Ex vivo, DCs develop from CD34(+) progenitors cultu red 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 clin ically relevant antigens and inducing active immunity in patients. Tar geting antigens to DCs may become feasible also because of the identif ication of distinct antigen receptors such as DEC-205, a DECalectin wi th 10 contiguous, C-type lectin domains. DEC-205 can mediate adsorptiv e uptake and presentation via DCs. AIDS is another disease for which D Cs should be considered in designing new therapies, since DCs can play a major role in promoting HIV-1 replication. Many HIV-1 isolates indu ce syncytia between DCs and CD4(+) memory T cells. These syncytia in t urn are the site for a productive infection with HIV-1, possibly becau se requisite transcription factors like NF-kappa B and Sp1 are separat ely provided by DCs and T cells, respectively. Further attention to th e DC lineage should provide new avenues for manipulating the immune sy stem in several clinical contexts.