Rat pancreatic islet pretreatment with anti-MHC class II monoclonal antibodies and culture: in vitro MLIC test response does not predict islet allograft survival.
Antigen presenting cells (APC) expressing MHC class II antigens have been attributed with stimulatory capacity for initiating islet allograft rejection (direct pathway). Therefore, we evaluated the effect of pretreating isolated islets with different monoclonal antibodies against MHC class II antigens and complement, with and without culture at 22 degrees C or 37 degrees C, on MHC class II antigen expression, on the allogeneic proliferative response in the mixed lymphocyte islet culture (MLIC) and on islet allograft survival in adult rats. Experiments were performed in two different strain combinations incompatible for MHC class II antigens and either incompatible or compatible for MHC class I antigens, in order to elucidate further the impact of class I antigens on islet allograft rejection. In terms of class II antigen suppression, pretreatment with anti-MHC class II antibodies together with complement and a 5-day (37 degrees C) culture period proved most effective. After this procedure 92.7% of the islets of LEW rats and 91.1% of the islets of LEW.1WR2 rats were negative for MHC class II antigens, as demonstrated by indirect immunofluorescence. Transfer of successfully pretreated islets to a MLIC in vitro test system provoked a significantly reduced allogeneic T-cell proliferative response in the case of additional MHC class I disparity (ratio 1.3 vs 4.7) and a response as low as that of a syngeneic setting when stimulator islets and allogeneic responder lymphocytes shared MHC class I antigens (ratio 1.0 vs 1.6).(ABSTRACT TRUNCATED AT 250 WORDS)
Bretzel
R G
RG
Third Medical Department, University of Giessen, Germany.
Flesch
B K
BK
Brennenstuhl
G
G
Greiner
I
I
Hering
B J
BJ
Woehrle
M
M
Federlin
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002478:Cells, Cultured; D006085:Graft Survival / Q000276:immunology*; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D000949:Histocompatibility Antigens Class II