ARYL HYDROCARBON RECEPTOR LIGANDS STIMULATE AUTO-REACTIVE TC1/TC17 T CELL ACTIVATION AND ENHANCE SELF-ANTIGEN-INDUCED DIABETES

In this paper, the effects of specific aryl-hydrocarbon receptor (AhR)-ligands, and the ligand precursor, tryptophan, on CD8+ T cell mediated autoimmunity were investigated for the first time using the RIP-LCMV-GP transgenic diabetes model. The authors find that the co-injection of tryptophan, curcumin, or quercetin together with immunization with mature bone marrow-derived dendritic cells carrying self-antigen, increased the incidence of diabetes induced in RIP-GP/P14 TCR transgenic mice. In contrast, co-injection with the AhR-ligands FICZ and I3C failed to stimulate diabetes. The activation of diabetes following injection of tryptophan, curcumin, or quercetin, correlated with their ability to increase IL-17+CD8+ (Tc17) and IFN- gamma +CD8+ (Tc1) cell populations, in vivo. Furthermore, in vitro experiments showed that tryptophan, curcumin, or quercetin treatments directly promoted significantly increased Tc1 and Tc17 cell development. These novel findings indicate that some AhR-ligands can increase CD8+ T cell-mediated autoimmune responses by skewing T cell polarization towards effector subsets.