Tolerance of islet allografts induced by orthotopic liver transplantation.
BACKGROUND
The induction of immunological tolerance by orthotopic liver transplantation (OLT) is donor-specific. Moreover, after the acceptance of a liver, other organs are not rejected. The aim of this study is to clarify characteristics of the prolonged islet survival as a result of immunological tolerance which was induced following simultaneous OLT.


METHODS
About 2000 islets were isolated from F344 rats. OLT was performed from F344 rats to diabetic LEW rats. Then the islets were transplanted into the transplanted F344 livers of diabetic LEW rats. Survival of the pancreatic islet allografts and deposits of IgM and IgG in the transplanted liver and islets were investigated.


RESULTS
Survival time in the group with OLT (mean survival time: 46.4 +/- 38.2 days) was significantly longer than that without OLT (mean survival time: 8.1 +/- 0.8 days) (P < 0.01). Amount of serum antibody against donor lymphocytes was slightly higher in the group without OLT, and was very high in the group with OLT. Histologically, severe lymphocytic infiltration was observed in the Glisson's sheaths in the group with OLT. Islets were lodged, without lymphocytes inside, in small branches of the portal vein 7 days after transplantation. Immunohistologically, IgM and IgG deposits were found in the Glisson's sheaths and along sinusoids; however, they were not found in the islets.


CONCLUSIONS
Induction of immunological tolerance and long-term survival of islets are possible by simultaneous OLT. The mechanism of this tolerance could be the host's selection of the liver as a target of preferred immunological attack.
Sawada
T
T
Department of Surgery, Department of Pathology, Akita University School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
Asanuma
Y
Y
Furuya
T
T
Saito
K
K
Koyama
K
K
D000818:Animals; D001323:Autoantibodies / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000601:surgery; D006085:Graft Survival / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D007150:Immunohistochemistry; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D013997:Time Factors; D014181:Transplantation Immunology / Q000276:immunology
D001323:Autoantibodies; D001786:Blood Glucose; D007074:Immunoglobulin G; D007075:Immunoglobulin M