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Published July 17, 2023 | Version v1
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Tissue-specific features of the T cell repertoire following allogeneic hematopoietic cell transplantation in human and mouse

Authors/Creators

  • 1. Memorial Sloan Kettering Cancer Center
  • 2. Weill Cornell Medicine
  • 3. The University of Texas MD Anderson Cancer Center
  • 4. Fred Hutchinson Cancer Research Center

Description

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.

Notes

Data here are aggregated from the Adaptive Biotech data found here: https://doi.org/10.21417/SD2022GVHD

Funding provided by: National Institute on Aging
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000049
Award Number: P01-AG052359

Funding provided by: National Heart, Lung, and Blood Institute
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000050
Award Number: K08HL143189

Funding provided by: National Heart, Lung, and Blood Institute
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000050
Award Number: R01-HL123340

Funding provided by: National Heart, Lung, and Blood Institute
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000050
Award Number: R01-HL147584

Funding provided by: National Cancer Institute
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000054
Award Number: T32CA009512

Funding provided by: National Cancer Institute
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000054
Award Number: R01-CA228358

Funding provided by: National Cancer Institute
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000054
Award Number: R01-CA228308

Funding provided by: National Cancer Institute
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000054
Award Number: P01-CA023766

Funding provided by: National Cancer Institute
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000054
Award Number: P30 CA008748

Funding provided by: Parker Institute for Cancer Immunotherapy
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100014547
Award Number:

Funding provided by: American Society of Clinical Oncology
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100006293
Award Number: Young Investigator Award

Funding provided by: American Society for Transplantation and Cellular Therapy
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100015394
Award Number:

Funding provided by: American Society for Transplantation and Cellular Therapy
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100015394
Award Number:

Funding provided by: Deutsche Forschungsgemeinschaft
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100001659
Award Number:

Funding provided by: American Society of Hematology
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100001422
Award Number:

Funding provided by: Cycle for Survival
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100017050
Award Number:

Funding provided by: NHLBI Division of Intramural Research
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100017540
Award Number: R01-HL164902

Funding provided by: Memorial Sloan-Kettering Cancer Center
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100007052
Award Number:

Funding provided by: DKMS Foundation
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100020046
Award Number:

Funding provided by: Tri Institutional Stem Cell Initiative
Award Number:

Funding provided by: Lymphoma Foundation
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100007043
Award Number:

Funding provided by: The Susan and Peter Solomon Divisional Genomics Program
Award Number:

Funding provided by: Memorial Sloan-Kettering Cancer Center
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100007052
Award Number:

Funding provided by: Memorial Sloan-Kettering Cancer Center
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100007052
Award Number: NIH/NCI P50 CA254838-01

Funding provided by: Memorial Sloan-Kettering Cancer Center
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100007052
Award Number:

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Additional details

Related works

Is supplemented by
10.21417/SD2022GVHD (DOI)