Citation

Background Dendritic cells (DC) induce adaptive responses against foreign antigens, and play an essential role in maintaining peripheral tolerance to self-antigens. Therefore they are involved in preventing fatal autoimmunity. Selective delivery of antigens to immature DC via the endocytic DEC-205 receptor on their surface promotes antigen-specific T cell tolerance, both by recessive and dominant mechanisms. We provide evidence that the induction of antigen-specific T cell tolerance is not a unique property of CD11c+CD8+DEC-205+ DCs. Methods We employed a fusion between DCIR2 antibodies and the highly encephalitogenic peptide 139151 of myelin-derived proteolipid protein (PLP139151), to target CD11c +CD8- DCs with a DEC-205DCIR2+ phenotype in vivo, and to substantially improve clinical symptoms in the PLP139151-induced model of experimental autoimmune encephalomyelitis (EAE). Results Consistent with previous studies targeting other cell surface receptors, EAE protection mediated by DCIR2-PLP139151 fusion antibody (Ab) depended on an immature state of targeted DCIR2+ DCs. The mechanism of DCIR2-PLP139151 mAb function included the deletion of IL-17- and IFN–producing pathogenic T cells, as well as the enhancement of regulatory T (Treg) cell activity. In contrast to the effect of DEC-205+ fusion antibodies, which involves extrathymic induction of a Foxp3+ Treg cell phenotype in nave CD4+Foxp3- T cells, treatment of animals with DCIR2+ fusion antibodies resulted in antigen-specific activation and proliferative expansion of natural Foxp3+ Treg cells. Conclusions These results suggest that multiple mechanisms can lead to the expansion of the Treg population, depending on the DC subset and receptor targeted.