Identical α-chain T-cell receptor transcripts are present on T cells infiltrating coronary arteries of human cardiac allografts with chronic rejection

Chronic cardiac allograft rejection is characterized by graft arteriopathy and is a major obstacle of graft survival. We investigated T-cell receptor (TCR) α-chain transcripts of T cells infiltrating human epicardial coronary arteries from cardiac allografts with chronic rejection. The non-palindromic adaptor-polymerase chain reaction (NPA-PCR) was used to specifically amplify TCR α-chain transcripts from five explanted cardiac allografts with chronic rejection. The amplified products were cloned and sequenced to obtain the entire VαJα region. Immuno-histochemistry was used to identify the mononuclear cell infiltrates in the coronary arteries. All the five coronary artery specimens exhibited large populations of infiltrating mononuclear cells, which were primarily comprised of T cells and macrophages. In three specimens, high proportions (∼80%) of identical α-chain TCR transcripts were detected. In peripheral blood mononuclear cells from a healthy individual, α-chain TCR transcripts were unique when compared to each other. Endomyocardial biopsies collected from one patient six months before the allograft was explanted, contained identical α-chain TCR transcripts to those found to be clonally expanded in the coronary arteries from this patient. These results indicate that T cells infiltrating the epicardial arteries of cardiac allografts with chronic rejection undergo proliferation and clonal expansion in response to a specific antigen, which very likely is an (allo)antigen(s).