Comment

Identifying the factors that determine Th1 versus Th2 lymphocyte differentiation is the goal of many scientists, and in recent years it seemed that a modicum of understanding was finally within reach. Contributions from many different sources have helped to determine beyond reasonable doubt that it is the local cytokine microenvironment that plays the most important role in directing T helper cell differentiation during the immune response.1 Text books and journals are full of good examples of how Th0 cells are directed towards a Th1 phenotype by cytokines such as interleukin (IL) 12, whereas cytokines like IL-4 promote differentiation towards a Th2 phenotype. Furthermore, it is well accepted that the Th1 cells produce cytokines that will encourage more Th0 cells towards a Th1 differentiation pathway, and likewise the Th2 cells produce cytokines that direct more Th0 cells towards a Th2 differentiation pathway. Although these positive autocrine mechanisms make sense in the context of an ongoing immune response, the initial effects which cause a pool of naïve T cells to be driven selectively down a particular pathway are still not well understood. A recent study by Rissoan and colleagues may have brought us one step closer to understanding this phenomenon.

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 …