Viral infection induces de novo lesions of coronary allograft vasculopathy through a natural killer cell-dependent pathway.
Viral infections including those due to cytomegalovirus have been associated with accelerated cardiac allograft vasculopathy (CAV) in clinical trials and some animal models. Evidence demonstrating a direct causal relationship between such infections and de novo formation of coronary vascular lesions is lacking. Heterotopic murine cardiac transplants were performed in a parental to F1 combination in animals lacking both T- and B-lymphocytes (RAG(-/-)). Coronary vasculopathy developed almost exclusively in the presence of recipient infection with lymphocytic choriomeningitis virus but not in uninfected controls. This process was also dependent upon the presence of natural killer (NK) cells as depletion of NK cells abrogated the process. These data show that a viral infection in its native host, and not previously implicated in the production of CAV, can contribute to the development of advanced coronary vascular lesions in cardiac allotransplants in mice. These data also suggest that virus-induced CAV can develop via an NK-cell-dependent pathway in the absence of T- and B-lymphocytes.
Transplantation Research Division, Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
J A
JA
Graham
R A
RA
Wilkinson
T
T
Hirohashi
C M
CM
Chase
R B
RB
Colvin
J C
JC
Madsen
J A
JA
Fishman
P S
PS
Russell
D000818:Animals; D001117:Arenaviridae Infections / Q000150:complications / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D003327:Coronary Disease / Q000276:immunology / Q000821:virology*; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation; D018398:Homeodomain Proteins / Q000235:genetics; D016867:Immunocompromised Host; D007694:Killer Cells, Natural / Q000276:immunology / Q000821:virology*; D008217:Lymphocytic choriomeningitis virus; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D013601:T-Lymphocytes / Q000276:immunology; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
D018398:Homeodomain Proteins; C064658:RAG-1 protein