Time frame of pancreas allograft rejection: an immunogenetic analysis in MHC-disparate, presensitized inbred rat strains.
OBJECTIVE
The pattern of rejection of vascularized pancreas allografts in presensitized recipients was studied among congeneic and recombinant rat strains in order to establish the time frame of rejection. Donors and recipients differed either in their entire MHC or in class I or class II MHC antigens.


METHODS
Streptozotocin diabetic (55 mg/kg bone weight) recipients underwent an intra-abdominal heterotopic pancreas whole organ transplantation. The exocrine secretion of the pancreas was suppressed by ligation of the duct. Rejection was defined as recurrence of diabetic hyperglycemia exceeding 14 mmol/L, which was subsequently confirmed by histologic examination. The pancreas recipients were presensitized by repetitive donor-specific skin transplants performed 12, 8, and 4 weeks prior to pancreas grafting.


RESULTS
The results shown accelerated rejection in all instances. Animals with incompatibility for the entire MHC showed a median rejection time in naive recipients of 12.5 days and in presensitized recipients of 8 days. Class I MHC incompatible native recipients rejected the allografts after 16.5 days (median) and presensitized recipients after 9 days (median). Concerning class II MHC incompatibility rejection appeared in naive recipients after 16 days (median) and in presensitized recipients after 7 days (median). Hyperacute rejection, however, was not observed.


CONCLUSIONS
These results show an accelerated pattern of rejection in all instances caused by donor MHC antigens. Hyperacute rejection, however, was not observed. The effect is slightly pronounced in class II MHC incompatibility. Acceleration of rejection may be caused by stimulation of the humoral as well as the cellular pathway of the immune response. The underlying mechanisms concerning the different MHC incompatibilities, however, remain speculative.
Litmathe
J
J
Department of Surgery-Clinic B, Heinrich-Heine University of Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, Federal Republic of Germany. litmathe@med.uni-duesseldorf.de
Bektas
H
H
Jörns
A
A
Klempnauer
J
J
D000818:Animals; D000906:Antibodies / Q000097:blood; D000917:Antibody Formation; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000473:pathology*; D006085:Graft Survival / Q000276:immunology*; D006650:Histocompatibility Testing; D007518:Isoantibodies / Q000097:blood; D016035:Pancreas Transplantation / Q000276:immunology* / Q000473:pathology / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D016038:Skin Transplantation / Q000276:immunology
D000906:Antibodies; D001786:Blood Glucose; D007518:Isoantibodies