Induction of donor major histocompatibility complex antigens in coronary arterial vessels: Mechanism of arterial vasculitis in rat allografts treated with cyclosporine

A. Herskowitz, F. Tamura, K. Ueda, D. A. Neumann, M. Slepian, N. R. Rose, W. E. Beschorner, W. A. Baumgartner, B. R. Reitz, K. W. Sell, A. Ahmed-Ansari

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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 mroe 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.

Original languageEnglish (US)
Pages (from-to)11-19
Number of pages9
JournalJournal of Heart Transplantation
Volume8
Issue number1
StatePublished - Jan 1 1989
Externally publishedYes

ASJC Scopus subject areas

  • Transplantation

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