Faculty, Staff and Student Publications

Publication Date

7-26-2023

Journal

Science Translational Medicine

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

Humans, Mice, Animals, T-Lymphocytes, Hematopoietic Stem Cell Transplantation, Graft vs Host Disease, Receptors, Antigen, T-Cell

DOI

10.1126/scitranslmed.abq0476

PMID

37494469

PMCID

PMC10758167

PubMedCentral® Posted Date

January 2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

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