Cytokines and rejection of mouse cardiac allografts.
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.
Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City 84143, USA.
J F
JF
Carlquist
L S
LS
Edelman
W
W
White
J
J
Shelby
J L
JL
Anderson
D019264:Adoptive Transfer; D000818:Animals; D001803:Blood Transfusion; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology*; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival; D016027:Heart Transplantation / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology; D016019:Survival Analysis
D016207:Cytokines; D007371:Interferon-gamma