title: The combi-effect--reduced rejection of the heart by combined transplantation with the lung or spleen.
abstract: The term combi-effect was introduced to describe the phenomenon of a reduction in rejection of heart grafts after combined transplantation with the lung. In this study in rats we investigated whether the combi-effect was an immunological process and whether it could also be induced by combined transplantation of the heart with the spleen or with a lymphocyte-depleted spleen. Heart and spleen grafts were transplanted into the abdomen; left lungs were transplanted into the thorax of recipient rats. To deplete spleens of their lymphocytes, prospective donor rats were irradiated. Cyclosporine was injected once, on day 2 after transplantation. All heart allografts transplanted alone and treated with cyclosporine were rejected acutely (median survival time [MST] of 14.5 days). In contrast, after combined transplantation of a donor lung or spleen with the heart, almost all heart grafts survived indefinitely. Transplantation of a syngeneic lung or third-party spleen had little effect on heart graft survival (MST of 22.5 days and 26.5 days, respectively). Without cyclosporine treatment, combined transplantation with a donor lung or spleen hardly prolonged heart graft survival. Transplantation of a lymphocyte-depleted spleen with the heart induced a combi-effect in cyclosporine-treated rats that was somewhat weaker: only two of six hearts survived indefinitely. We conclude that in the combi-effect an immunological mechanism reduces rejection of the heart. This mechanism is probably generated by the lymphoid tissue (bronchus-associated lymphoid tissue in lung and white pulp in spleen) in the combined transplant.
authors.affiliation: Cardiopulmonary Surgery Research Division, Thoraxcentrum, University Hospital Groningen, The Netherlands.
authors.forename: A L
authors.initials: AL
authors.lastname: Westra
authors.forename: A H
authors.initials: AH
authors.lastname: Petersen
authors.forename: J
authors.initials: J
authors.lastname: Prop
authors.forename: C R
authors.initials: CR
authors.lastname: Wildevuur
mesh_terms: D000818:Animals; D006084:Graft Rejection; D006085:Graft Survival / Q000502:physiology; D016041:Heart-Lung Transplantation / Q000276:immunology*; D008212:Lymphocyte Depletion; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013154:Spleen / Q000473:pathology / Q000637:transplantation*