Dendritic cell subsets: the ultimate T cell differentiation decision makers?

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Abstract
Rissoan et al make a very good argument that Th cell differentiation is controlled by specific dendritic cell (DC) subsets. The authors describe two major DC subsets—monocyte derived DC1 cells and plasmacytoid derived DC2 cells which, as their names suggest, are purported to drive Th1 and Th2 differentiation, respectively. These DC subsets are apparently able to drive differentiation of naïve Th0 cells down the Th1 or Th2 pathways independently of the cytokines that were traditionally believed to be important. DC1 cells secrete copious amounts of IL-12, thus creating a microenvironment conducive to Th1 cell differentiation, but the authors clearly show that DC1 cells can induce Th1 differentiation even in the absence of IL-12. A striking argument for Th differentiation being mediated by specific interactions with DC subsets and not cytokines comes from analysis of DC2 cells. DC2 cells selectively direct Th0 cells towards a Th2 phenotype, yet seem to be totally devoid of IL-4. Although the selectivity of the DC1 and DC2 subsets for driving Th1 and Th2 responses seems to be definitive, there is as yet no insight into the precise mechanism driving the differentiation. It will be interesting to learn whether these DC subsets mediate their activity via direct cell–cell contact or via novel soluble mediators.