Differential regulation of dendritic cell–T cell cross talk in the gut-associated lymphoid tissue

Dendritic cells (DC) play a central role in the regulation of immune responses by processing and presenting antigens to naïve T cells. It has been proposed that after the initial interaction between DC and T cells, T cell-induced DC apoptosis serves as a down-regulatory mechanism that prevents the otherwise continuous activation of T cells by antigen-bearing DC. Our aim was to investigate and compare the susceptibility of Peyer's patch (PP)-derived and systemic (splenic) DC to antigen-specific T cell-mediated apoptosis in mice of different genetic background. Freshly isolated CD11c+/hiB220− DC from intestinal Peyer's patch and spleen from Balb/c and C3H/HeJ mice were co-cultured with syngeneic antigen-specific T cells in the presence or absence of the relevant antigen. In both mouse strains PP-DC showed higher susceptibility to T cell-mediated apoptosis compared to splenic ones, but levels of DC apoptosis were overall higher in C3H/HeJ mice compared to Balb/c. DC apoptosis was induced by both Th1 and Th2 antigen-specific clones and was strictly MHC class II-dependent in both strains, and interestingly we observed that although CD95-CD95L ligation played an overall minor part in T cell-induced DC apoptosis its role varied according to the mouse strain. Here, we demonstrated that PP-DC and splenic DC significantly differed in regard to their susceptibility to T cell-mediated killing. We interpreted these data as showing that the reciprocal regulation between DC and T cells in the gastrointestinal immune system is under stricter control compared to the systemic immune system and we hypothesized that these events are likely to contribute to the generation of fine balanced responses to intestinal antigens.