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 m odel we observed that C3H (H-2k) recipients infected with murine CMV ( MCMV) rejected BALB/c (H-2d) cardiac allografts earlier than uninfecte d recipients (6.9+/-0.1 d compared with 8.1+/-0.6 d; P < 0.001). It ha s been hypothesized that MCMV epitopes crossreact with alloantigens an d in this manner induce rejection. However, we also demonstrated that MCMV caused accelerated rejection in the reverse combination (C3H hear t engrafted to BALB/c recipient; 7.2+/-0.3 and 9.4+/-0.4 d for infecte d and control animals, respectively; P < 0.00 1) and accelerated rejec tion 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 t he time of graft rejection, were almost exclusively CD8+ for both infe cted and control recipients. Thus, MCMV accelerated rejection appears not to result from crossreaction between MCMV epitopes and MHC product s. The failure of UV-inactivated virus to accelerate rejection and the high proportion of CD8+ T cells recovered from all rejected grafts su ggest that the class I pathway of antigen presentation may be importan t in the induction of early rejection.