title: Induction of donor major histocompatibility complex antigens in coronary arterial vessels: mechanism of arterial vasculitis in rat allografts treated with cyclosporine.
abstract: Recently, a potentially lethal pattern of vascular rejection has been described in heart transplant patients treated with cyclosporine. The purpose of this study was to identify potential immune mechanisms responsible for the development of coronary vascular injury associated with acute rejection. Our hypothesis was that changes in histocompatibility (MHC) expression induced by immunosuppressive therapy with cyclosporine plays an important role in directing an immune response to the arterial bed. With the ACI to Lewis allograft model, we compared the histology and immunohistology of both unmodified allograft rejection at days 2, 3, and 4 after transplantation, and allograft rejection modified by pretreatment with cyclosporine. Both models exhibit histologic evidence of early rejection before extensive myocyte necrosis is seen. Unmodified early rejection develops rapidly and is associated with dense MHC class I antigen expression on both myocytes and venous endothelium. Cyclosporine-modified rejection develops more slowly and is characterized by an arterial vasculitis. This modified pattern of rejection is associated with increased myocardial expression of MHC class II antigens with the arterial bed preferentially expressing increased MHC antigens. It is interesting to speculate that in the setting of a slower developing rejection process, the preferential expression of MHC antigens within the arterial bed produces a delayed-type hypersensitivity response directed toward either the endothelium and/or adjacent MHC class II expressing myocytes. A prolonged periarterial and intraluminal inflammatory reaction may then produce a true vasculitis, which may be detrimental to the survival of the graft.
authors.affiliation: Department of Immunology and Infectious Diseases, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: A
authors.initials: A
authors.lastname: Herskowitz
authors.forename: F
authors.initials: F
authors.lastname: Tamura
authors.forename: K
authors.initials: K
authors.lastname: Ueda
authors.forename: D A
authors.initials: DA
authors.lastname: Neumann
authors.forename: M
authors.initials: M
authors.lastname: Slepian
authors.forename: N R
authors.initials: NR
authors.lastname: Rose
authors.forename: W E
authors.initials: WE
authors.lastname: Beschorner
authors.forename: W A
authors.initials: WA
authors.lastname: Baumgartner
authors.forename: B R
authors.initials: BR
authors.lastname: Reitz
authors.forename: K W
authors.initials: KW
authors.lastname: Sell
mesh_terms: D000818:Animals; D001167:Arteritis / Q000276:immunology / Q000503:physiopathology*; D003327:Coronary Disease / Q000276:immunology / Q000503:physiopathology*; D003331:Coronary Vessels / Q000276:immunology*; D003524:Cyclosporins / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006084:Graft Rejection / Q000187:drug effects; D016027:Heart Transplantation; D006649:Histocompatibility Antigens / Q000032:analysis / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000235:genetics; D008285:Major Histocompatibility Complex; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D003524:Cyclosporins; D006649:Histocompatibility Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II