Tissue-specific features of the T cell repertoire after allogeneic hematopoietic cell transplantation in human and mouse Journal Article

   

Authors:	DeWolf, S.; Elhanati, Y.; Nichols, K.; Waters, N. R.; Nguyen, C. L.; Slingerland, J. B.; Rodriguez, N.; Lyudovyk, O.; Giardina, P. A.; Kousa, A. I.; Andrlová, H.; Ceglia, N.; Fei, T.; Kappagantula, R.; Li, Y.; Aleynick, N.; Baez, P.; Murali, R.; Hayashi, A.; Lee, N.; Gipson, B.; Rangesa, M.; Katsamakis, Z.; Dai, A.; Blouin, A. G.; Arcila, M.; Masilionis, I.; Chaligne, R.; Ponce, D. M.; Landau, H. J.; Politikos, I.; Tamari, R.; Hanash, A. M.; Jenq, R. R.; Giralt, S. A.; Markey, K. A.; Zhang, Y.; Perales, M. A.; Socci, N. D.; Greenbaum, B. D.; Iacobuzio-Donahue, C. A.; Hollmann, T. J.; van den Brink, M. R. M.; Peled, J. U.
Article Title:	Tissue-specific features of the T cell repertoire after allogeneic hematopoietic cell transplantation in human and mouse
Abstract:	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.
Keywords:	t lymphocyte; t-lymphocytes; mouse; animal; animals; mice; hematopoietic stem cell transplantation; pathology; receptors, antigen, t-cell; graft versus host reaction; graft vs host disease; lymphocyte antigen receptor; humans; human
Journal Title:	Science Translational Medicine
Volume:	15
Issue:	706
ISSN:	1946-6234
Publisher:	American Association for the Advancement of Science
Date Published:	2023-07-26
Start Page:	eabq0476
Language:	English
DOI:	10.1126/scitranslmed.abq0476
PUBMED:	37494469
PROVIDER:	scopus
PMCID:	PMC10758167
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85165929097&doi=10.1126%2fscitranslmed.abq0476&partnerID=40&md5=2954e1995c5dbace3983152a924c72f4
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK author is Jonathan U. Peled -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/208842