Accelerated rejection of murine cardiac allografts by murine cytomegalovirus-infected recipients. Lack of haplotype specificity.
Clinical studies have revealed a correlation between cytomegalovirus (CMV) infection and acute allograft rejection. Likewise, for a murine model we observed that C3H (H-2k) recipients infected with murine CMV (MCMV) rejected BALB/c (H-2d) cardiac allografts earlier than uninfected recipients (6.9 +/- 0.1 d compared with 8.1 +/- 0.6 d; P < 0.001). It has been hypothesized that MCMV epitopes crossreact with alloantigens and in this manner induce rejection. However, we also demonstrated that MCMV caused accelerated rejection in the reverse combination (C3H heart engrafted to BALB/c recipient; 7.2 +/- 0.3 and 9.4 +/- 0.4 d for infected and control animals, respectively; P < 0.001) and accelerated rejection of grafts of a third, unrelated haplotype (C57Bl/6; H-2b; 8.0 +/- 0.7 d compared with 10.1 +/- 0.6 for infected and control C3H recipients, respectively; P < 0.03). Ultraviolet (UV) inactivation of MCMV before administration to the graft recipient abrogated the ability to induce rapid rejection. Activated T lymphocytes were present in grafts from infected recipients 2 d before control recipients (P < 0.02) and, at the time of graft rejection, were almost exclusively CD8+ for both infected and control recipients. Thus, MCMV accelerated rejection appears not to result from crossreaction between MCMV epitopes and MHC products. The failure of UV-inactivated virus to accelerate rejection and the high proportion of CD8+ T cells recovered from all rejected grafts suggest that the class I pathway of antigen presentation may be important in the induction of early rejection.
Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City.
J F
JF
Carlquist
J
J
Shelby
Y L
YL
Shao
J H
JH
Greenwood
M E
ME
Hammond
J L
JL
Anderson
D000818:Animals; D002465:Cell Movement; D003586:Cytomegalovirus Infections / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival; D006239:Haplotypes; D016027:Heart Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors