Inhibition of chronic rejection by antibody induced vascular accommodation in fully allogeneic heart allografts

Natalya V. Semiletova, Xiu Da Shen, Boris Baibakov, Daniel M. Feldman, Kaushik Mukherjee, Jonathan M. Frank, Stainslaw M. Stepkowski, Ronald W. Busuttil, Jerzy W. Kupiec-Weglinski, Rafik M. Ghobrial

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Background. The potential role of altered antibody responses as an effector protective mechanism to induce graft accommodation has been widely investigated in xenogeneic responses. Here we investigate the protective effects of antibody binding to vascular endothelium in a fully mismatched allogeneic model of heart transplantation. Methods. ACI recipients of WF cardiac grafts were treated either with allochimeric [α1h 1/u]-RT1.Aa class I major histocompatibility complex (MHC) extracts (1 mg/rat, p.v. day 0) or high dose of CsA (10 mg/kg/day, p.o., day 0-6). Cardiac allografts were evaluated at 100 days posttransplant by immunohistology for evidence of chronic rejection and/or vascular accommodation. Activation of apoptotic or antiapoptotic mechanisms was verified by DNA fragmentation (TUNEL) analysis. Results. Allochimeric therapy resulted in inhibition of chronic rejection, absence of neointimal formation and induction of vascular accommodation of fully allogeneic WF hearts in ACI hosts. Such accommodation was evident by IgG and IgM vascular endothelial binding and marked reduction of DNA fragmentation. In contrast, CsA therapy resulted in marked neointimal proliferation, without evidence of vascular accommodation. Immunohistochemical analysis failed to demonstrate vascular endothelial antibody binding. Further, severe chronic rejection following CsA treatment was accompanied by marked DNA fragmentation. Conclusion. Alteration of humoral immunity induces vascular accommodation in allogeneic transplantation. Vascular accommodation is the underlying mechanism for inhibition allograft vasculopathy following allochimeric MHC class I therapy.

Original languageEnglish (US)
Pages (from-to)1535-1540
Number of pages6
JournalTransplantation
Volume80
Issue number11
DOIs
StatePublished - Dec 2005

Keywords

  • Accommodation
  • Alloantibody
  • Allochimeric protein
  • Heart transplant
  • MHC class I

ASJC Scopus subject areas

  • Transplantation
  • Immunology

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