Progression of alloresponse and tissue-specific immunity during graft coronary artery disease

Masashi Tanaka, Monika Zwierzchoniewska, Golnaz K. Mokhtari, Raya D. Terry, Leora B. Balsam, Robert C. Robbins, Eugenia V. Fedoseyeva

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Chronic rejection remains the major obstacle for long-term transplant survival. Both indirect alloresponse and tissue-specific autoimmunity have been implicated in its pathogenesis. The interrelationship between these two types of host anti-graft response remains poorly understood. We have developed an immunosuppression-free mouse model of graft coronary artery disease (GCAD), in which all FVB (H-2q) cardiac allografts placed into minor Ag (mHC)-mismatched DBA/1 (H-2q) hosts survived more than 112 days, and developed GCAD. We then examined the kinetics of both anti-mHC alloresponse and host autoimmunity against heart-specific antigen, cardiac myosin (CM). At 8 days post-transplantation, recipient mice showed minimal intragraft inflammation and apoptosis, and limited expansion of allo-specific T cells. In addition, we observed early production of anti-myosin IgG1 autoantibodies, which occurred in the absence of activated CM-specific T lymphocytes. By day 56, GCAD indices, the numbers of mHC- and CM-reactive T cells, and the levels of circulating allo-and CM-specific antibodies were all significantly increased. While host alloresponse was exhausted at 112 days post-transplant, T-cell reactivity against CM persisted. Our data suggest that both allo- and tissue-specific immunity might contribute to the induction of GCAD. They indicate that continual autoimmune response against graft tissue antigens may provide for GCAD sustenance.

Original languageEnglish (US)
Pages (from-to)1286-1296
Number of pages11
JournalAmerican Journal of Transplantation
Volume5
Issue number6
DOIs
StatePublished - Jun 2005
Externally publishedYes

Keywords

  • Cardiac myocin
  • Graft coronary artery disease
  • Indirect alloresponse
  • Minor histocompatibility complex
  • Tissue-specific autoimmunity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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