Heart Transplant Research Today is a free monthly online journal that collates and summarizes the latest research about Heart Transplant, including details on risks, prognosis, procedure, surgery, organ donation.

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

Tanaka M, Zwierzchoniewska M, Mokhtari GK, Terry RD, Balsam LB, Robbins RC, Fedoseyeva EV

Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA 94305-5407, USA. masashi@omiya.jichi.ac.ap

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-2(q)) cardiac allografts placed into minor Ag (mHC)-mismatched DBA/1 (H-2(q)) 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.

Published 12 May 2005 in Am J Transplant, 5(6): 1286-96.
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