Dynamic establishment of recipient resident memory T cell repertoire after human intestinal transplantation.
Dynamic reconstitution
Human intestinal transplantation (ITx)
T cell receptor (TCR) repertoire
TCRβ sequencing
Tissue resident memory T cells (TRM)
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Mar 2024
Mar 2024
Historique:
received:
07
02
2023
revised:
19
01
2024
accepted:
06
02
2024
medline:
18
3
2024
pubmed:
1
3
2024
entrez:
29
2
2024
Statut:
ppublish
Résumé
Understanding formation of the human tissue resident memory T cell (TRM) repertoire requires longitudinal access to human non-lymphoid tissues. By applying flow cytometry and next generation sequencing to serial blood, lymphoid tissue, and gut samples from 16 intestinal transplantation (ITx) patients, we assessed the origin, distribution, and specificity of human TRMs at phenotypic and clonal levels. Donor age ≥1 year and blood T cell macrochimerism (peak level ≥4%) were associated with delayed establishment of stable recipient TRM repertoires in the transplanted ileum. T cell receptor (TCR) overlap between paired gut and blood repertoires from ITx patients was significantly greater than that in healthy controls, demonstrating increased gut-blood crosstalk after ITx. Crosstalk with the circulating pool remained high for years of follow-up. TCR sequences identifiable in pre-Tx recipient gut but not those in lymphoid tissues alone were more likely to populate post-Tx ileal allografts. Clones detected in both pre-Tx gut and lymphoid tissue had distinct transcriptional profiles from those identifiable in only one tissue. Recipient T cells were distributed widely throughout the gut, including allograft and native colon, which had substantial repertoire overlap. Both alloreactive and microbe-reactive recipient T cells persisted in transplanted ileum, contributing to the TRM repertoire. Our studies reveal human intestinal TRM repertoire establishment from the circulation, preferentially involving lymphoid tissue counterparts of recipient intestinal T cell clones, including TRMs. We have described the temporal and spatial dynamics of this active crosstalk between the circulating pool and the intestinal TRM pool. This study was funded by the National Institute of Allergy and Infectious Diseases (NIAID) P01 grant AI106697.
Sections du résumé
BACKGROUND
BACKGROUND
Understanding formation of the human tissue resident memory T cell (TRM) repertoire requires longitudinal access to human non-lymphoid tissues.
METHODS
METHODS
By applying flow cytometry and next generation sequencing to serial blood, lymphoid tissue, and gut samples from 16 intestinal transplantation (ITx) patients, we assessed the origin, distribution, and specificity of human TRMs at phenotypic and clonal levels.
FINDINGS
RESULTS
Donor age ≥1 year and blood T cell macrochimerism (peak level ≥4%) were associated with delayed establishment of stable recipient TRM repertoires in the transplanted ileum. T cell receptor (TCR) overlap between paired gut and blood repertoires from ITx patients was significantly greater than that in healthy controls, demonstrating increased gut-blood crosstalk after ITx. Crosstalk with the circulating pool remained high for years of follow-up. TCR sequences identifiable in pre-Tx recipient gut but not those in lymphoid tissues alone were more likely to populate post-Tx ileal allografts. Clones detected in both pre-Tx gut and lymphoid tissue had distinct transcriptional profiles from those identifiable in only one tissue. Recipient T cells were distributed widely throughout the gut, including allograft and native colon, which had substantial repertoire overlap. Both alloreactive and microbe-reactive recipient T cells persisted in transplanted ileum, contributing to the TRM repertoire.
INTERPRETATION
CONCLUSIONS
Our studies reveal human intestinal TRM repertoire establishment from the circulation, preferentially involving lymphoid tissue counterparts of recipient intestinal T cell clones, including TRMs. We have described the temporal and spatial dynamics of this active crosstalk between the circulating pool and the intestinal TRM pool.
FUNDING
BACKGROUND
This study was funded by the National Institute of Allergy and Infectious Diseases (NIAID) P01 grant AI106697.
Identifiants
pubmed: 38422982
pii: S2352-3964(24)00063-X
doi: 10.1016/j.ebiom.2024.105028
pmc: PMC10944178
pii:
doi:
Substances chimiques
Receptors, Antigen, T-Cell
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
105028Informations de copyright
Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests J.F. serves as a Scientific Consultant for Adaptive Biotechnologies Corp. since June 2022. A.O. serves as a Scientific Consultant for Janssen Pharmaceuticals and served as a Scientific Consultant for Enable Medicine.
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