Virus-specific TRM cells of both donor and recipient origin reside in human kidney transplants
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 hu...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2023-11-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.172681 |
| _version_ | 1797634263338713088 |
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| author | Daphne M. Hullegie-Peelen Hector Tejeda Mora Dennis A. Hesselink Eric M.J. Bindels Thierry P.P. van den Bosch Marian C. Clahsen-van Groningen Marjolein Dieterich Sebastiaan Heidt Robert C. Minnee Georges M.G.M. Verjans Martin J. Hoogduijn Carla C. Baan |
| author_facet | Daphne M. Hullegie-Peelen Hector Tejeda Mora Dennis A. Hesselink Eric M.J. Bindels Thierry P.P. van den Bosch Marian C. Clahsen-van Groningen Marjolein Dieterich Sebastiaan Heidt Robert C. Minnee Georges M.G.M. Verjans Martin J. Hoogduijn Carla C. Baan |
| author_sort | Daphne M. Hullegie-Peelen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T12:06:14Z |
| format | Article |
| id | doaj.art-fb29d72fe9e1487c9936e377474c2faa |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-03-11T12:06:14Z |
| publishDate | 2023-11-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-fb29d72fe9e1487c9936e377474c2faa2023-11-07T16:26:22ZengAmerican Society for Clinical investigationJCI Insight2379-37082023-11-01821Virus-specific TRM cells of both donor and recipient origin reside in human kidney transplantsDaphne M. Hullegie-PeelenHector Tejeda MoraDennis A. HesselinkEric M.J. BindelsThierry P.P. van den BoschMarian C. Clahsen-van GroningenMarjolein DieterichSebastiaan HeidtRobert C. MinneeGeorges M.G.M. VerjansMartin J. HoogduijnCarla C. BaanTissue-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.https://doi.org/10.1172/jci.insight.172681ImmunologyTransplantation |
| spellingShingle | Daphne M. Hullegie-Peelen Hector Tejeda Mora Dennis A. Hesselink Eric M.J. Bindels Thierry P.P. van den Bosch Marian C. Clahsen-van Groningen Marjolein Dieterich Sebastiaan Heidt Robert C. Minnee Georges M.G.M. Verjans Martin J. Hoogduijn Carla C. Baan Virus-specific TRM cells of both donor and recipient origin reside in human kidney transplants JCI Insight Immunology Transplantation |
| title | Virus-specific TRM cells of both donor and recipient origin reside in human kidney transplants |
| title_full | Virus-specific TRM cells of both donor and recipient origin reside in human kidney transplants |
| title_fullStr | Virus-specific TRM cells of both donor and recipient origin reside in human kidney transplants |
| title_full_unstemmed | Virus-specific TRM cells of both donor and recipient origin reside in human kidney transplants |
| title_short | Virus-specific TRM cells of both donor and recipient origin reside in human kidney transplants |
| title_sort | virus specific trm cells of both donor and recipient origin reside in human kidney transplants |
| topic | Immunology Transplantation |
| url | https://doi.org/10.1172/jci.insight.172681 |
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