@article{52897b5f726b40f3bf0954246453a407,
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.",
author = "Susan DeWolf and Yuval Elhanati and Katherine Nichols and Waters, {Nicholas R.} and Nguyen, {Chi L.} and Slingerland, {John B.} and Natasia Rodriguez and Olga Lyudovyk and Giardina, {Paul A.} and Kousa, {Anastasia I.} and Hana Andrlov{\'a} and Nick Ceglia and Teng Fei and Rajya Kappagantula and Yanyun Li and Nathan Aleynick and Priscilla Baez and Rajmohan Murali and Akimasa Hayashi and Nicole Lee and Brianna Gipson and Madhumitha Rangesa and Zoe Katsamakis and Anqi Dai and Blouin, {Amanda G.} and Maria Arcila and Ignas Masilionis and Ronan Chaligne and Ponce, {Doris M.} and Landau, {Heather J.} and Ioannis Politikos and Roni Tamari and Hanash, {Alan M.} and Jenq, {Robert R.} and Giralt, {Sergio A.} and Markey, {Kate A.} and Yanming Zhang and Perales, {Miguel Angel} and Socci, {Nicholas D.} and Greenbaum, {Benjamin D.} and Iacobuzio-Donahue, {Christine A.} and Hollmann, {Travis J.} and {van den Brink}, {Marcel R.M.} and Peled, {Jonathan U.}",
note = "Funding Information: This study would not have been possible without the generous donation of the patients and their families. We thank N. Mohibullah, A. Farina, and C. Cobbs for guidance and contribution with DNA preparation. We thank R. O{\textquoteright}Reilly and J. Steinman for helpful data discussions. S.D.W. reports research funding from the National Cancer Institute Clinical Scholars T32 (T32CA009512), American Society of Clinical Oncology Young Investigator Award, MSK Leukemia SPORE Career Enhancement Program (NIH/NCI P50 CA254838-01), and MSK Gerstner Physician Scholar Program. H.A. reports research funding from the American Society for Transplantation and Cellular Therapy (ASTCT) and Deutsche Forschungsgemeinschaft (DFG). K.A.M. reports funding from DKMS Foundation and the American Society for Hematology. M.R.M.v.d.B. reports research funding from National Cancer Institute award numbers R01-CA228308, P30 CA008748 MSK Cancer Center Support Grant/Core Grant, and P01-CA023766; National Heart, Lung, and Blood Institute (NHLBI) award numbers R01-HL123340 and R01-HL147584; National Institute on Aging award number P01-AG052359; and Tri-Institutional Stem Cell Initiative. Additional funding was received from the Lymphoma Foundation, the Susan and Peter Solomon Family Fund, the Solomon Microbiome Nutrition and Cancer Program, Cycle for Survival, Parker Institute for Cancer Immunotherapy, Paula and Rodger Riney Multiple Myeloma Research Initiative, Starr Cancer Consortium, and Seres Therapeutics (M.R.M.v.d.B.). J.U.P. reports research funding from the ASTCT, MSKCC Cancer Systems Immunology Pilot Grant, and National Heart, Lung, and Blood Institute of Health Award K08HL143189. Publisher Copyright: Copyright {\textcopyright} 2023 The Authors, some rights reserved;",
year = "2023",
month = jul,
day = "26",
doi = "10.1126/scitranslmed.abq0476",
language = "English (US)",
volume = "15",
journal = "Science translational medicine",
issn = "1946-6234",
publisher = "American Association for the Advancement of Science",
number = "706",
}