CYTOKINES AND REJECTION OF MOUSE CARDIAC ALLOGRAFTS1

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Abstract
Graft survival is prolonged by pretransplant transfusion of the graft recipient. It has been postulated that graft rejection is associated with Th1-like cytokines. We tested whether transfusion shifts cytokine production from a Th1-type (γ-IFN production) to a Th2-type (IL-4 production). Transfusion prolonged cardiac allograft (C3H/HeN donor to a C57BL/6 recipient) survival (10.4±0.5 versus 7.2±0.2 days for controls, P<0.0001). Splenocyte cultures from nontransfused recipients produced supernatant IFN-γ concentrations of 13.4±1.4 ng/ml upon anti-CD3 stimulation; the same cells produced 32.3±3.5 pg/ml IL-4 stimulated with Con A. Spleen cells from transfused animals did not produce γ-IFN with or without stimulation;(P<0.0001) and produced 21.5±3.2 pg/ml IL-4 without stimulation (P<0.0001 compared with controls). C57BL/6 CD8+ lymphocytes isolated from rejected C3H grafts were adoptively transferred(6.7±1×106/animal) to pretransfused, C57BL/6 recipients of a C3H graft. Graft survival for these recipients was 7.8±0.3 days compared with 10.4±0.5 days for recipients pretreated with transfusion only (P<0.005). Transcripts of the γ-IFN gene were present in unmodified grafts but not in the grafts from transfused recipients given the CD8 cells. In conclusion, transfusion downregulated γ-IFN production and up-regulated IL-4 production and slowed (but did not abrogate) rejection; CD8 graft-infiltrating cells given adoptively restored normal rejection but not IFN-γ. Further studies are needed to elucidate the role of cytokines in cardiac allograft rejection.