Since their discovery in 1973 by Zanvil Cohn and Ralph Steinman, dendritic cells (DCs) have gained increased interest among immunologists, as these cells display unique properties aimed at inducing an immune response against antigens that invade the organism. They perform multiple tasks with high efficiency, and appear to determine the specificity, magnitude and nature (Th1/Th2) of the immune response.In the mouse, two subclasses of dendritic cells have been described that differ by their CD8á expression and their localization in lymphoid organs.We have assessed the function of both subclasses in vivo by injecting purified DC, pulsed extracorporeally with antigen, into the footpads of syngeneic mice and analyzing the immune response of lymph node cells. Our data show that both DC subsets efficiently prime antigen-specific T cells in vivo, and direct the development of distinct T helper cell populations. Administration of CD8á- DC induces a Th2-type response, whereas injection of CD8á+ DC leads to Th1 differentiation. Th1 priming is dependent on IL-12 production by DCs.These findings suggest that the nature of the DC that presents the antigen to naive T cells may dictate the class selection of the adaptive immune response. Experiments are under way to assess the role of various DC populations in activating the recently discovered Th17 cell population, which plays a role in autoimmune and allergic inflammation. More recently, a number of reports have shown that, in addition to their well known stimulatory properties, DCs may play a major role in peripheral tolerance. It is still unclear whether a distinct subtype or activation status of DC exists which promotes the differentiation of suppressor rather than effector T cells from naive precursors. We tested whether the naturally occurring CD4+CD25+ regulatory T cells may control immune responses induced by DCs in vivo. We found that the development of IFN-a-producing cells and cytotoxic T cells was strongly enhanced in the absence of regulatory T cells. By contrast, Th2 priming was downregulated in the same conditions. Collectively, these observations suggest that the function of mature DCs is under the tight control of the naturally occurring CD4+CD25+ cells in vivo and that regulatory T cells influence the character of T cell differentiation by selectively dampening Th1-type responses and CTLs. [Since their discovery in 1973 by Zanvil Cohn and Ralph Steinman, dendritic cells (DCs) have gained increased interest among immunologists, as these cells display unique properties aimed at inducing an immune response against antigens that invade the organism. They perform multiple tasks with high efficiency, and appear to determine the specificity, magnitude and nature (Th1/Th2) of the immune response.In the mouse, two subclasses of dendritic cells have been described that differ by their CD8á expression and their localization in lymphoid organs.We have assessed the function of both subclasses in vivo by injecting purified DC, pulsed extracorporeally with antigen, into the footpads of syngeneic mice and analyzing the immune response of lymph node cells. Our data show that both DC subsets efficiently prime antigen-specific T cells in vivo, and direct the development of distinct T helper cell populations. Administration of CD8á- DC induces a Th2-type response, whereas injection of CD8á+ DC leads to Th1 differentiation. Th1 priming is dependent on IL-12 production by DCs.These findings suggest that the nature of the DC that presents the antigen to naive T cells may dictate the class selection of the adaptive immune response. Experiments are under way to assess the role of various DC populations in activating the recently discovered Th17 cell population, which plays a role in autoimmune and allergic inflammation. More recently, a number of reports have shown that, in addition to their well known stimulatory properties, DCs may play a major role in peripheral tolerance. It is still unclear whether a distinct subtype or activation status of DC exists which promotes the differentiation of suppressor rather than effector T cells from naive precursors. We tested whether the naturally occurring CD4+CD25+ regulatory T cells may control immune responses induced by DCs in vivo. We found that the development of IFN-a-producing cells and cytotoxic T cells was strongly enhanced in the absence of regulatory T cells. By contrast, Th2 priming was downregulated in the same conditions. Collectively, these observations suggest that the function of mature DCs is under the tight control of the naturally occurring CD4+CD25+ cells in vivo and that regulatory T cells influence the character of T cell differentiation by selectively dampening Th1-type responses and CTLs.]