Coronary arteries from human cardiac allografts with chronic rejection contain oligoclonal T cells: Persistence of identical clonally expanded TCR transcripts from the early post-transplantation period (endomyocardial biopsies) to chronic rejection (coronary arteries)

Chronic cardiac allograft rejection presents pathologically as graft arteri osclerosis (GA) characterized by recipient T cell and monocyte infiltration . To determine whether oligoclonal T cells are present in coronary arteries of cardiac allografts from patients with GA, we conducted sequencing analy sis of beta -chain TCR transcripts from these explanted coronary arteries u sing the nonpalindromic adaptor-PCR, Substantial proportions of identical b eta -chain TCR transcripts in three of five patients were observed, clearly demonstrating the presence of oligoclonal T cells. TCR transcripts from th e arteries of two other patients were relative heterogeneous. High proporti ons of identical CDR3 beta -chain TCR motifs were found in each patient. GE NEBANK/EMBL/SWISS PROT database comparison of all sequences revealed that t hese beta -chain TCR transcripts were novel. Using VP-specific PCR (indepen dent amplification), we found in patient GA03 that the TCR transcript that was clonally expanded in the left anterior descending artery after nonpalin dromic adaptor-PCR was also clonally expanded in the right coronary artery of the same allograft, These results demonstrate that this TCR transcript w as clonally expanded at different anatomic sides of the cardiac allograft i n a systemic manner. In two patients identical beta -chain TCR transcripts that were found to be clonally expanded in the coronary arteries of their e xplanted cardiac allografts were also found to be clonally explanted in end omyocardial biopsies collected 17 and 21 mo earlier from each patient. The presence of oligoclonal populations of T cells in the rejected graft sugges t that these T cells have undergone specific Ag-driven proliferation and cl onal expansion early on within the graft and persist throughout the post-tr ansplantation period.