The mammalian immune system has evolved distinct strategies for defending itself from a wide variety of pathogens, which range from single-cell microorganisms to large parasitic worms. One of its most potent responses is mediated by CD4+ T helper (Th) cells, which can differentiate into specific effector cells with characteristic cytokine profiles.
Dendritic cells (DCs) are instrumental in driving the appropriate differentiation of Th cells. They patrol the tissue and serve as sentinels against invading pathogens. Upon activation, they migrate to the draining lymph nodes to drive the development of the appropriate adaptive immune response. However, it remains unclear if different populations of DCs are specialised to induce a particular Th cell response or if environmental conditioning influence DCs in their phenotype and function.
To understand the roles of DC subset specialisation and environmental conditioning in the context of Th cell differentiation, we performed a side-by-side comparison of DCs exposed to bacterial, fungal or helminthic antigens in vivo. Our data showed that while each antigen drove a distinct CD4 T cell response, antigen was transported to the lymph nodes by the same populations of CD326-CD103- DCs. Antigen-carrying DCs were key to the priming of Th cell responses and showed a selective up-regulation of co-stimulatory molecules. The deletion of CD326+ and CD103+ DC subsets had no impact on the resulting CD4 T cell response but the transfer of antigen-carrying DCs was sufficient to drive the appropriate Th cell responses. Furthermore, transcriptional profiling of sorted antigen-positive DCs showed distinct cytokine and chemokine profiles when exposed to different sources of antigens, which were important for the differentiation of the appropriate Th cells.
Thus, our data suggest that DCs are conditioned by the environment and produce specific cytokines and chemokines to promote the appropriate differentiation of CD4 T cells to defend against particular pathogens.