Xu Bin, Sakkas Lazaros I, Goldman Bruce I, Jeevanandam Valluvan, Gaughan John, Oleszak Emilia L, Platsoucas Chris D
Department of Microbiology and Immunology, The Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Cell Immunol. 2003 Oct;225(2):75-90. doi: 10.1016/j.cellimm.2003.10.002.
Chronic cardiac allograft rejection is characterized by graft arteriopathy and is a major obstacle of graft survival. We investigated T-cell receptor (TCR) alpha-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 alpha-chain transcripts from five explanted cardiac allografts with chronic rejection. The amplified products were cloned and sequenced to obtain the entire ValphaJalpha 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 ( approximately 80%) of identical alpha-chain TCR transcripts were detected. In peripheral blood mononuclear cells from a healthy individual, alpha-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 alpha-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).
慢性心脏移植排斥反应的特征是移植血管病，是影响移植物存活的主要障碍。我们研究了慢性排斥反应心脏移植中浸润人心外膜冠状动脉的T细胞的T细胞受体（TCR）α链转录本。采用非回文衔接子聚合酶链反应（NPA-PCR）从5例慢性排斥反应的心脏移植切除标本中特异性扩增TCRα链转录本。对扩增产物进行克隆和测序，以获得完整的VαJα区域。采用免疫组织化学方法鉴定冠状动脉中的单核细胞浸润情况。所有5例冠状动脉标本均显示大量浸润的单核细胞，主要由T细胞和巨噬细胞组成。在3例标本中，检测到高比例（约80%）相同的α链TCR转录本。在健康个体的外周血单核细胞中，α链TCR转录本彼此不同。在移植心脏切除前6个月从1例患者采集的心肌内膜活检标本中，含有与该患者冠状动脉中克隆性扩增的α链TCR转录本相同的转录本。这些结果表明，浸润慢性排斥反应心脏移植心外膜动脉的T细胞在特定抗原（很可能是一种（同种）抗原）刺激下发生增殖和克隆性扩增。
