title: Human coronary transplantation-associated arteriosclerosis. Evidence for a chronic immune reaction to activated graft endothelial cells.
abstract: Occlusive disease of coronary arteries of engrafted hearts is the major obstacle to long-term survival of human cardiac allografts. The pathogenesis of this process remains uncertain. The identity and localization of cells found in transplantation-associated arteriosclerosis lesions from human cardiac allografts were evaluated, and their expression of class II major histocompatibility complex (human leukocyte antigen-DR [HLA-DR]), surface molecules required for recognition of foreign cells by CD4+ T lymphocytes, was noted. Expanded intimas of transplanted coronary arteries contain T lymphocytes (both CD4+ and CD8+ in approximately equal number) and HLA-DR+ macrophages, both localized primarily in a ring immediately below the luminal endothelium, a distribution strikingly different from that in typical atherosclerosis. Coronary arterial endothelium from six of six transplanted hearts studied bore high levels of HLA-DR. Normal human arteries or usual atherosclerotic lesions have few if any HLA-DR+ endothelial cells. The significance of these findings was tested by evaluating the ability of HLA-DR+ arterial cells to interact with allogeneic T cells in vitro. Endothelial cells (but not smooth muscle cells) cultured from human arteries stimulated foreign CD4+ T cells to proliferate and augmented their secretion of interleukin-2. These findings suggest that ongoing stimulation of recipient T lymphocytes by HLA-DR+ endothelium of donor coronary arteries contributes to a sustained regional immune response. Consequent local release of cytokines may regulate smooth muscle cell proliferation and matrix accumulation within the coronary arteries of allografted hearts.
authors.affiliation: Department of Pathology, New England Medical Center, Boston, Massachusetts.
authors.forename: R N
authors.initials: RN
authors.lastname: Salomon
authors.forename: C C
authors.initials: CC
authors.lastname: Hughes
authors.forename: F J
authors.initials: FJ
authors.lastname: Schoen
authors.forename: D D
authors.initials: DD
authors.lastname: Payne
authors.forename: J S
authors.initials: JS
authors.lastname: Pober
authors.forename: P
authors.initials: P
authors.lastname: Libby
mesh_terms: D015704:CD4 Antigens / Q000032:analysis; D003324:Coronary Artery Disease / Q000209:etiology*; D003331:Coronary Vessels / Q000473:pathology; D004730:Endothelium, Vascular / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D006680:HLA Antigens / Q000276:immunology; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007107:Immune System / Q000503:physiopathology*; D009131:Muscle, Smooth, Vascular / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology
chemical_list: D015704:CD4 Antigens; D006680:HLA Antigens