Virus-specific TRM Cells of Both Donor and Recipient Origin Reside in Human Kidney Transplants

Overview

Journal JCI Insight

Specialties Biomedical Engineering
General Medicine

Date 2023 Sep 26

PMID 37751288

Authors

Daphne M Hullegie-Peelen

Hector Tejeda Mora

Dennis A Hesselink

Eric Mj Bindels

Thierry Pp van den Bosch

Marian C Clahsen-van Groningen

Marjolein Dieterich

Sebastiaan Heidt

Robert C Minnee

Georges Mgm Verjans

Martin J Hoogduijn

Carla C Baan

Affiliations

Soon will be listed here.

Abstract

Tissue-resident lymphocytes (TRLs) are critical for local protection against viral pathogens in peripheral tissue. However, it is unclear if TRLs perform a similar role in transplanted organs under chronic immunosuppressed conditions. In this study, we aimed to characterize the TRL compartment in human kidney transplant nephrectomies and examine its potential role in antiviral immunity. The TRL compartment of kidney transplants contained diverse innate, innate-like, and adaptive TRL populations expressing the canonical residency markers CD69, CD103, and CD49a. Chimerism of donor and recipient cells was present in 43% of kidney transplants and occurred in all TRL subpopulations. Paired single-cell transcriptome and T cell receptor (TCR) sequencing showed that donor and recipient tissue-resident memory T (TRM) cells exhibit striking similarities in their transcriptomic profiles and share numerous TCR clonotypes predicted to target viral pathogens. Virus dextramer staining further confirmed that CD8 TRM cells of both donor and recipient origin express TCRs with specificities against common viruses, including CMV, EBV, BK polyomavirus, and influenza A. Overall, the study results demonstrate that a diverse population of TRLs resides in kidney transplants and offer compelling evidence that TRM cells of both donor and recipient origin reside within this TRL population and may contribute to local protection against viral pathogens.

Citing Articles

Donor HLA-DQ genetic and functional divergence affect the control of BK polyoma virus infection after kidney transplantation.

Chevalier M, Allain V, Gras J, Racle J, Villemonteix J, Divard G Sci Adv. 2025; 11(10):eadt3499.

PMID: 40043107 PMC: 11881896. DOI: 10.1126/sciadv.adt3499.

Kidney immunology from pathophysiology to clinical translation.

Kurts C, von Vietinghoff S, Krebs C, Panzer U Nat Rev Immunol. 2025; .

PMID: 39885266 DOI: 10.1038/s41577-025-01131-y.

Cellular Immunity Against BK Polyomavirus in Kidney Transplant Recipients: A Comprehensive Review.

Al-Talib M, Skaria A, Griffin S Transpl Infect Dis. 2024; 27(1):e14401.

PMID: 39499036 PMC: 11827742. DOI: 10.1111/tid.14401.

References

Zheng M, Wakim L . Tissue resident memory T cells in the respiratory tract. Mucosal Immunol. 2021; 15(3):379-388. PMC: 8526531. DOI: 10.1038/s41385-021-00461-z. View

Tian G, Li M, Lv G . Analysis of T-Cell Receptor Repertoire in Transplantation: Fingerprint of T Cell-mediated Alloresponse. Front Immunol. 2022; 12:778559. PMC: 8790170. DOI: 10.3389/fimmu.2021.778559. View

Nin N, Lorente J, Sanchez-Rodriguez C, Granados R, Ver L, Soto L . Kidney histopathological findings in fatal pandemic 2009 influenza A (H1N1). Intensive Care Med. 2011; 37(5):880-1. PMC: 7095449. DOI: 10.1007/s00134-011-2183-7. View

Kumar B, Ma W, Miron M, Granot T, Guyer R, Carpenter D . Human Tissue-Resident Memory T Cells Are Defined by Core Transcriptional and Functional Signatures in Lymphoid and Mucosal Sites. Cell Rep. 2017; 20(12):2921-2934. PMC: 5646692. DOI: 10.1016/j.celrep.2017.08.078. View

Parga-Vidal L, van Aalderen M, Stark R, van Gisbergen K . Tissue-resident memory T cells in the urogenital tract. Nat Rev Nephrol. 2022; 18(4):209-223. DOI: 10.1038/s41581-021-00525-0. View

Zhang W, Wang L, Liu K, Wei X, Yang K, Du W . PIRD: Pan Immune Repertoire Database. Bioinformatics. 2019; 36(3):897-903. DOI: 10.1093/bioinformatics/btz614. View

Diniz M, Mitsi E, Swadling L, Rylance J, Johnson M, Goldblatt D . Airway-resident T cells from unexposed individuals cross-recognize SARS-CoV-2. Nat Immunol. 2022; 23(9):1324-1329. PMC: 9477726. DOI: 10.1038/s41590-022-01292-1. View

Borcherding N, Bormann N, Kraus G . scRepertoire: An R-based toolkit for single-cell immune receptor analysis. F1000Res. 2020; 9:47. PMC: 7400693. DOI: 10.12688/f1000research.22139.2. View

Christo S, Evrard M, Park S, Gandolfo L, Burn T, Fonseca R . Discrete tissue microenvironments instruct diversity in resident memory T cell function and plasticity. Nat Immunol. 2021; 22(9):1140-1151. DOI: 10.1038/s41590-021-01004-1. View

10.

Carmona F, Carlotti A, N Z Ramalho L, Costa R, Ramalho F . Evidence of Renal Infection in Fatal Cases of 2009 Pandemic Influenza A (H1N1). Am J Clin Pathol. 2011; 136(3):416-23. DOI: 10.1309/AJCP1Y6LLHWSKYHW. View

11.

Gasteiger G, Fan X, Dikiy S, Lee S, Rudensky A . Tissue residency of innate lymphoid cells in lymphoid and nonlymphoid organs. Science. 2015; 350(6263):981-5. PMC: 4720139. DOI: 10.1126/science.aac9593. View

12.

Clute S, Naumov Y, Watkin L, Aslan N, Sullivan J, Thorley-Lawson D . Broad cross-reactive TCR repertoires recognizing dissimilar Epstein-Barr and influenza A virus epitopes. J Immunol. 2010; 185(11):6753-64. PMC: 3738202. DOI: 10.4049/jimmunol.1000812. View

13.

Soto C, Bombardi R, Kozhevnikov M, Sinkovits R, Chen E, Branchizio A . High Frequency of Shared Clonotypes in Human T Cell Receptor Repertoires. Cell Rep. 2020; 32(2):107882. PMC: 7433715. DOI: 10.1016/j.celrep.2020.107882. View

14.

Snyder M, Finlayson M, Connors T, Dogra P, Senda T, Bush E . Generation and persistence of human tissue-resident memory T cells in lung transplantation. Sci Immunol. 2019; 4(33). PMC: 6435356. DOI: 10.1126/sciimmunol.aav5581. View

15.

Gomez-Massa E, Lasa-Lazaro M, Gil-Etayo F, Ulloa-Marquez E, Justo I, Loinaz C . Donor helper innate lymphoid cells are replaced earlier than lineage positive cells and persist long-term in human intestinal grafts - a descriptive study. Transpl Int. 2020; 33(9):1016-1029. DOI: 10.1111/tri.13609. View

16.

Kaminski H, Couzi L, Eberl M . Unconventional T cells and kidney disease. Nat Rev Nephrol. 2021; 17(12):795-813. DOI: 10.1038/s41581-021-00466-8. View

17.

Kanehisa M, Furumichi M, Sato Y, Kawashima M, Ishiguro-Watanabe M . KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res. 2022; 51(D1):D587-D592. PMC: 9825424. DOI: 10.1093/nar/gkac963. View

18.

Prosser A, Huang W, Liu L, Dart S, Watson M, De Boer B . Dynamic changes to tissue-resident immunity after MHC-matched and MHC-mismatched solid organ transplantation. Cell Rep. 2021; 35(7):109141. DOI: 10.1016/j.celrep.2021.109141. View

19.

van Aalderen M, Remmerswaal E, Heutinck K, Ten Brinke A, Feltkamp M, van der Weerd N . Clinically Relevant Reactivation of Polyomavirus BK (BKPyV) in HLA-A02-Positive Renal Transplant Recipients Is Associated with Impaired Effector-Memory Differentiation of BKPyV-Specific CD8+ T Cells. PLoS Pathog. 2016; 12(10):e1005903. PMC: 5056763. DOI: 10.1371/journal.ppat.1005903. View

20.

Sun H, Sun C, Xiao W, Sun R . Tissue-resident lymphocytes: from adaptive to innate immunity. Cell Mol Immunol. 2019; 16(3):205-215. PMC: 6460493. DOI: 10.1038/s41423-018-0192-y. View