Pretreatment of rat pancreatic islets with MHC I-A monoclonal antibody: in-vitro and in-vivo effects on islet antigenicity.
Pancreatic islet allografts are rejected very rapidly due to their high immunogenicity. Several attempts have been made to reduce the immunogenicity prior to transplantation. We treated islets with MHC Ia (class II) antigen monoclonal antibody and complement in order to lyse Ia antigen bearing cells within the islets. This treatment caused a distinct reduction of Ia antigen positive cells, which was demonstrated by indirect immunofluorescence tests. A total depletion of the Ia antigens, however, could not be achieved. As a second in-vitro test to evaluate the effect of the antibody treatment a mixed lymphocyte islet culture (MLIC) was performed. The partial Ia antigen reduction provoked a significantly reduced but not completely suppressed allogenic T-cell response. Antibody treatment did neither impair the morphological integrity nor the function of the islets as could be demonstrated by syngenic transplantation of islets pretreated by antibodies in the same way. After allotransplantation of antibody-pretreated islets across a major histocompatibility barrier into non immunosuppressed rats, however, there was no significant prolongation of the graft survival. Thus, a partial reduction of the number of the Ia antigen positive cells within the islets is not sufficient for the prevention of allograft rejection.
Flesch
B K
BK
Medizinische Klinik III, Justus-Liebig-Universität, Giessen, Germany.
Bretzel
R G
RG
Otto
D A
DA
Ernst-Schlegel
M
M
Federlin
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D006085:Graft Survival; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000276:immunology*; D007515:Islets of Langerhans / Q000276:immunology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D008212:Lymphocyte Depletion; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D012016:Reference Values; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
D000911:Antibodies, Monoclonal; D000949:Histocompatibility Antigens Class II