Autoimmune sensitization to cardiac myosin leads to acute rejection of cardiac allografts in miniature swine

Gregory R. Veillette, Hisashi Sahara, Andrew J. Meltzer, Mathew J. Weiss, Yoshiko Iwamoto, Karen M. Kim, Bruce R. Rosengard, James S. Allan, Stuart L. Houser, David H. Sachs, Gilles Benichou, Joren C. Madsen

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Recent studies in mice and patients suggest that posttransplantation induction of autoimmune responses to tissue-specific antigens contributes to the rejection of major histocompatibility complex mismatched allotransplants. The relevance of this phenomenon to the rejection of major and minor histocompatibility-mismatched allografts performed in large-animal models remains to be established. Methods: Miniature swine were immunized with cardiac myosin (CM) in Freund's adjuvant and received heterotopic, minor antigen-mismatched heart transplants. T-cell (proliferation and delayed type hypersensitivity [DTH]) and B-cell (antibody) responses specific to CM were measured. The rejection of heart transplants was assessed histologically. Results: Three of four swine that were immunized with CM before receiving a minor antigen-mismatched heart transplant exhibited potent DTH, T-cell proliferation and antibody responses to CM and rejected their grafts acutely. The fourth swine, which failed to mount a significant DTH response to CM and displayed low and transient anti-CM antibody titers, demonstrated long-term allograft survival. Conclusions: This large-animal study supports the relevance of autoimmunity to CM in the rejection of minor antigen disparate cardiac allotransplants.

Original languageEnglish (US)
Pages (from-to)1187-1191
Number of pages5
JournalTransplantation
Volume91
Issue number11
DOIs
StatePublished - Jun 15 2011

Keywords

  • Autoimmunity
  • Cardiac myosin
  • Heart transplantation
  • Swine

ASJC Scopus subject areas

  • Transplantation

Fingerprint Dive into the research topics of 'Autoimmune sensitization to cardiac myosin leads to acute rejection of cardiac allografts in miniature swine'. Together they form a unique fingerprint.

Cite this