Selective Depletion of Cross-Presenting Dendritic Cells Enhances Islet Allograft Survival

Abstract

MHC class I presentation of peptides derived from exogenous antigens (not synthesized within the antigen-presenting cell) is called cross-presentation and is mediated by selective subsets of dendritic cells (DC). A proportion of both donor and host DC may cross-present. Although there has been many studies that have investigated the role of donor versus host DC (i.e., direct vs. indirect pathway), what role cross-presenting DC play in allograft rejection has not been determined. We recently identified an agent, cytochrome c (cytc), that selectively depletes cross-presenting DC in vivo. By administering cytc we were able to study the impact of cross-presenting DC on rejection of islets grafted into fully mismatched mice. We found that cytc protected about half of the islet allografts from rejection. Our results indicate that cross-presenting DC can make potent contributions to the immune response to islet allografts, and contend that agents such as cytc that selectively target DC heralds a novel method of immunosuppression.