Identical alpha-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) 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).
Xu
Bin
B
Department of Microbiology and Immunology, The Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Sakkas
Lazaros I
LI
Goldman
Bruce I
BI
Jeevanandam
Valluvan
V
Gaughan
John
J
Oleszak
Emilia L
EL
Platsoucas
Chris D
CD
D002465:Cell Movement / Q000276:immunology; D003331:Coronary Vessels / Q000276:immunology* / Q000473:pathology; D014644:Genetic Variation; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014184:Transplantation, Homologous
D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell