Major histocompatibility complex antigens and murine islet allograft survival.
Immunomodulation of rodent islets can significantly prolong allograft survival. We utilized a murine model of primary islet transplantation to study the relationship between allograft survival and the quantitative pretransplant expression of class I and II MHC antigens in freshly isolated CBA/J islets, and islets subjected to 37 degrees C tissue culture, brief culture at 7 degrees C, or exposure of the donor to lipopolysaccharide. Seven-day culture resulted in decreased class II expression, a tendency to decreased class I expression, and a significant prolongation of allograft survival. Brief culture at 7 degrees C resulted in increased class I expression, a trend to decreased class II expression, and no significant change in allograft survival. Donor pretreatment with LPS resulted in increased class I expression without significant change in class II expression and was correlated with prolongation of allograft survival. These studies demonstrate that an upregulation of MHC class I by in vitro or in vivo islet pretreatment is not associated with an acceleration of islet rejection. Reduction of class II was associated with delayed rejection. These results do not support a major role of the indirect pathway of antigen presentation in islet rejection in vivo. Certain protocols that alter the usual expression of class I and II on pancreatic islets are associated with alteration in the initiation and/or propagation of the normal cell-mediated rejection process, suggesting that the concept of pretransplant treatment should continue to be pursued.
Kneteman
N M
NM
Department of Surgery, University of Alberta, Edmonton, Canada.
Halloran
P F
PF
Sanden
W D
WD
Wang
T
T
Seelis
R E
RE
D000818:Animals; D006085:Graft Survival; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D007515:Islets of Langerhans / Q000276:immunology*; D016381:Islets of Langerhans Transplantation; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D014184:Transplantation, Homologous
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides