The mammalian immune system is confronted by a wide variety of pathogens, ranging from single-cell organisms such as bacteria and yeasts to large parasitic worms. The ability to control and clear these diverse infections is strictly dependent on the ability to mount the appropriate type of immune response. A major part of tailoring the immune response for optimal infection resolution involves the differentiation of naïve CD4+ T helper (Th) cells into effector cells with characteristic cytokine profiles.

Migratory tissue-derived dendritic cells (migDC) play an important role in regulating the appropriate differentiation of Th cells in the draining lymph nodes (dLN) following pathogen encounter in the tissue. MigDC can be resolved into many distinct subsets, but the processes by which these subsets regulate Th cell differentiation are currently debated. Some evidence suggests that DC subsets are pre-programmed to induce a particular response upon activation, whereas other evidence points to an environmental conditioning process where factors such as signals from the antigen itself or from cells in the environment influence DC phenotype and function.

To understand the roles of migDC subset specialisation and environmental conditioning in the context of Th cell differentiation, we performed a side-by-side comparison of migDC exposed to a range of infectious antigens in vivo. Our data show that each antigen was able to drive a distinct CD4 T cell response, characterised by the expression of different cytokines and transcription factors by the responding CD4+ T cells. Antigen-carrying DC were key to the priming of T cell responses as shown by their strong and selective up-regulation of co-stimulatory molecules and increased transcription of cytokines and chemokines specific to each response. Interestingly, the variability in the migDC response was accompanied by a notable variability in other immune populations in the lymph node.