Tissue-specific features of the T cell repertoire following allogeneic hematopoietic cell transplantation in human and mouse
DOI10.5281/zenodo.8157543Zenodo8157543MaRDI QIDQ6683740
Dataset published at Zenodo repository.
Yuval Elhanati, Teng Fei, Nicholas Ceglia, Priscilla Baez, Robert Jenq, Kate Markey, Heather Landau, Anastasia Kousa, Susan Dewolf, Akimasa Hayashi, Hana Andrlova, Rajmohan Murali, Paul Giardina, Madhumitha Rangesa, Alan Hanash, Zoe Katsamakis, Ronan Chaligne, Katherine Nichols, Jonathan U Peled, Nicholas Socci, Miguel-Angel Perales, Christine Iacobuzio-Donahue, Nicole Lee, Brianna Gipson, Natasia Rodriguez, Maria Arcila, Nathan Aleynick, Rajya Kappagantula, Yanyun Li, Sergio Giralt, Anqi Dai, Yanming Zhang, Travis Hollmann, Amanda Blouin, Doris M Ponce, Ioannis Politikos, Chi Nguyen, Benjamin Greenbaum, Olga Lyudovyk, Ignas Masilionis, Nicholas R Waters, John Slingerland, Marcel R. M. Van Den Brink, Roni Tamari
Publication date: 17 July 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 (5-18 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, as well as 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 spleen 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 following lymphocyte-directed therapy. These findings also underscore the importance of studying T cells in tissues rather than blood for tissue-based pathologies and suggest the tissue-specific nature of both the endogenous and post-transplant T cell landscape.
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