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T cell repertoire analysis suggest a prominent bystander response in human cardiac allograft vasculopathy
- Source :
- Am J Transplant
- Publication Year :
- 2020
-
Abstract
- T cells are implicated in the pathogenesis of cardiac allograft vasculopathy (CAV), yet their clonality, specificity, and function are incompletely defined. Here we used T cell receptor β chain (TCRB) sequencing to study the T cell repertoire in the coronary artery, endomyocardium, and peripheral blood at the time of retransplant in four cases of CAV and compared it to the immunoglobulin heavy chain variable region (IGHV) repertoire from the same samples. High-dimensional flow cytometry coupled with single-cell PCR was also used to define the T cell phenotype. Extensive overlap was observed between intragraft and blood TCRBs in all cases, a finding supported by robust quantitative diversity metrics. In contrast, blood and graft IGHV repertoires from the same samples showed minimal overlap. Coronary infiltrates included CD4+ and CD8+ memory T cells expressing inflammatory (IFNγ, TNFα) and profibrotic (TGFβ) cytokines. These were distinguishable from the peripheral blood based on memory, activation, and tissue residency markers (CD45RO, CTLA-4, and CD69). Importantly, high-frequency rearrangements were traced back to endomyocardial biopsies (2-6 years prior). Comparison with four HLA-mismatched blood donors revealed a repertoire of shared TCRBs, including a subset of recently described cross-reactive sequences. These findings provide supportive evidence for an active local intragraft bystander T cell response in late-stage CAV.
- Subjects :
- Graft Rejection
T cell
T-Lymphocytes
030230 surgery
Article
Flow cytometry
Pathogenesis
03 medical and health sciences
0302 clinical medicine
Immunology and Allergy
Medicine
Humans
Pharmacology (medical)
Transplantation
medicine.diagnostic_test
business.industry
T-cell receptor
Allografts
Phenotype
Coronary Vessels
medicine.anatomical_structure
Immunology
Heart Transplantation
Tumor necrosis factor alpha
IGHV@
business
CD8
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Am J Transplant
- Accession number :
- edsair.doi.dedup.....8b7e15d32a4fcbfb2482379011e7877e