Tissue-specific features of the T cell repertoire after allogeneic hematopoietic cell transplantation in human and mouse.
Susan DeWolfYuval ElhanatiKatherine NicholsNicholas R WatersChi L NguyenJohn B SlingerlandNatasia RodriguezOlga LyudovykPaul A GiardinaAnastasia I KousaHana AndrlováNick CegliaTeng FeiRajya KappagantulaYanyun LiNathan AleynickPriscilla BaezRajmohan MuraliAkimasa HayashiNicole LeeBrianna GipsonMadhumitha RangesaZoe KatsamakisAngel DaiAmanda G BlouinMaria E ArcilaIgnas MasilionisRonan ChalignéDoris M PonceHeather J LandauIoannis PolitikosRoni TamariAlan M HanashRobert R JenqSergio A GiraltKate A MarkeyYanming ZhangMiguel-Ángel PeralesNicholas D SocciBenjamin D GreenbaumChristine A Iacobuzio-DonahueTravis J HollmanMarcel R M van den BrinkJonathan U PeledPublished in: Science translational medicine (2023)
T cells are the central drivers of many inflammatory diseases, but the repertoire of tissue-resident T cells at sites of pathology in human organs remains poorly understood. We examined the site-specificity of T cell receptor (TCR) repertoires across tissues (5 to 18 tissues per patient) in prospectively collected autopsies of patients with and without graft-versus-host disease (GVHD), a potentially lethal tissue-targeting complication of allogeneic hematopoietic cell transplantation, and in mouse models of GVHD. Anatomic similarity between tissues was a key determinant of TCR repertoire composition within patients, independent of disease or transplant status. The T cells recovered from peripheral blood and spleens in patients and mice captured a limited portion of the TCR repertoire detected in tissues. Whereas few T cell clones were shared across patients, motif-based clustering revealed shared repertoire signatures across patients in a tissue-specific fashion. T cells at disease sites had a tissue-resident phenotype and were of donor origin based on single-cell chimerism analysis. These data demonstrate the complex composition of T cell populations that persist in human tissues at the end stage of an inflammatory disorder after lymphocyte-directed therapy. These findings also underscore the importance of studying T cell in tissues rather than blood for tissue-based pathologies and suggest the tissue-specific nature of both the endogenous and posttransplant T cell landscape.
Keyphrases
- end stage renal disease
- ejection fraction
- single cell
- newly diagnosed
- chronic kidney disease
- gene expression
- endothelial cells
- prognostic factors
- peripheral blood
- peritoneal dialysis
- type diabetes
- machine learning
- stem cells
- stem cell transplantation
- patient reported outcomes
- low dose
- regulatory t cells
- acute lymphoblastic leukemia
- immune response
- case report
- rna seq
- quality improvement
- skeletal muscle
- patient safety
- dendritic cells
- mesenchymal stem cells
- dna methylation
- deep learning
- smoking cessation