Selective depletion of cross-presenting dendritic cells enhances islet allograft survival.
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.
Sutherland
Robyn M
RM
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne 3052, Victoria, Australia.
Zhan
Yifan
Y
Carrington
Emma M
EM
Londrigan
Sarah L
SL
Lew
Andrew M
AM
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D045142:Cross-Priming; D045304:Cytochromes c / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D006736:Horses; D007165:Immunosuppression Therapy; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013552:Swine; D014184:Transplantation, Homologous
D045304:Cytochromes c