CD8 alpha(+) and CD8 alpha(-) subclasses of dendritic cells direct the development of distinct T helper cells in vivo

Cells of the dendritic family display some unique properties that confer to them the capacity to sensitize naive T cells in vitro and in vivo. In the mouse, two subclasses of dendritic cells (DCs) have been described that dif fer by their CD8 alpha expression and their localization in lymphoid organs . The physiologic function of both cell populations remains obscure. Studie s conducted in vitro have suggested that CD8 alpha(+) DCs could play a role in the regulation of immune responses, whereas conventional CD8 alpha(-) D Cs would be more stimulatory. We report here that both subclasses of DCs ef ficiently prime antigen-specific T cells in vivo, and direct the developmen t of distinct T helper (Bh) populations. Antigen-pulsed CD8 alpha(+) and CD 8 alpha(-) DCs are separated after overnight culture in recombinant granulo cyte/macrophage colony-stimulating factor and injected into the footpads of syngeneic mice. Administration of CD8 alpha(-) DCs induces a Th2-type resp onse, whereas injection of CD8 alpha(+) DCs leads to Th1 differentiation. W e further show that interleukin 12 plays a critical role in Th1 development by CD8 alpha(+) DCs. These findings suggest that the nature of the DC that presents the antigen to naive T cells may dictate the class selection of t he adaptative immune response.