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Updated: Sep 13, 2026
Murine Heterotopic Heart Transplant Technique
Published on: July 8, 2014
Cytokines and rejection of mouse cardiac allografts
J F Carlquist1, L S Edelman, W White
1Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City 84143, USA.
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 (gamma-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-gamma 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 gamma-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+/-1x10(6)/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 gamma-IFN gene were present in unmodified grafts but not in the grafts from transfused recipients given the CD8 cells. In conclusion, transfusion downregulated gamma-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-gamma. Further studies are needed to elucidate the role of cytokines in cardiac allograft rejection.
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 (gamma-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-gamma 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 gamma-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+/-1x10(6)/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 gamma-IFN gene were present in unmodified grafts but not in the grafts from transfused recipients given the CD8 cells. In conclusion, transfusion downregulated gamma-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-gamma. Further studies are needed to elucidate the role of cytokines in cardiac allograft rejection.
