Pre-transplant T-cell clonal analysis identifies CD8+ donor reactive clones that contribute to kidney transplant rejection
IntroductionResponses to allogeneic human leukocyte antigen (HLA) molecules limit the survival of transplanted organs. The changes in T-cell alloreactivity that contribute to this process, however, are not fully understood. We defined a set of donor reactive T-cell clones (DRTC) with the goal to elu...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1516772/full |
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| author | Jes M. Sanders Barbara L. Banbury Erika L. Schumacher Jie He Yuvaraj Sambandam Paul A. Fields Lorenzo Gallon Lorenzo Gallon James M. Mathew James M. Mathew James M. Mathew Joseph R. Leventhal Joseph R. Leventhal |
| author_facet | Jes M. Sanders Barbara L. Banbury Erika L. Schumacher Jie He Yuvaraj Sambandam Paul A. Fields Lorenzo Gallon Lorenzo Gallon James M. Mathew James M. Mathew James M. Mathew Joseph R. Leventhal Joseph R. Leventhal |
| author_sort | Jes M. Sanders |
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| description | IntroductionResponses to allogeneic human leukocyte antigen (HLA) molecules limit the survival of transplanted organs. The changes in T-cell alloreactivity that contribute to this process, however, are not fully understood. We defined a set of donor reactive T-cell clones (DRTC) with the goal to elucidate signatures of kidney allograft rejection.MethodsDRTC were identified pretransplant using an anti-donor mixed lymphocyte reaction assay: CFSE-diluting CD4+ and CD8+ DRTC were flow-sorted, and the TCR sequences were identified using Adaptive Immunosequencing. DRTC were then tracked in post-transplant biopsies, blood, and urine samples in a cohort of kidney transplant recipients.ResultsIn patients with an abnormal biopsy, the majority of CD8+ DRTC found within the allograft were detected in the circulating pre-transplant repertoire. Circulating CD8+ DRTC were more abundant pre- and post-transplant in patients that received non-lymphodepletional induction and developed an abnormal biopsy when compared to stable patients. Additionally, DRTC were detected as early as two weeks post-transplant in the urine of some patients, with some of these clones subsequently identified in follow-up kidney biopsy samples.DiscussionThe findings of our study add to our understanding of T-cell alloreactivity following kidney transplantation and provide evidence for the role of pre-defined alloreactive T-cells in the development of allograft rejection. |
| format | Article |
| id | doaj-art-539cbcbd3dcf49e0aedbf4030e1803b7 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-539cbcbd3dcf49e0aedbf4030e1803b72025-02-06T12:20:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15167721516772Pre-transplant T-cell clonal analysis identifies CD8+ donor reactive clones that contribute to kidney transplant rejectionJes M. Sanders0Barbara L. Banbury1Erika L. Schumacher2Jie He3Yuvaraj Sambandam4Paul A. Fields5Lorenzo Gallon6Lorenzo Gallon7James M. Mathew8James M. Mathew9James M. Mathew10Joseph R. Leventhal11Joseph R. Leventhal12Department of Surgery, Division of Organ Transplantation, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, United StatesAdaptive Biotechnologies, Seattle, WA, United StatesAdaptive Biotechnologies, Seattle, WA, United StatesDepartment of Surgery, Division of Organ Transplantation, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, United StatesDepartment of Surgery, Division of Organ Transplantation, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, United StatesAdaptive Biotechnologies, Seattle, WA, United StatesDepartment of Medicine, Division of Nephrology, Northwestern University Feinberg School of Medicine, Chicago, IL, United StatesSimpson Querrey Institute for BioNanotechnology, Northwestern University Feinberg School of Medicine, Chicago, IL, United StatesDepartment of Surgery, Division of Organ Transplantation, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, United StatesSimpson Querrey Institute for BioNanotechnology, Northwestern University Feinberg School of Medicine, Chicago, IL, United StatesDepartment of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, United StatesDepartment of Surgery, Division of Organ Transplantation, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, United StatesSimpson Querrey Institute for BioNanotechnology, Northwestern University Feinberg School of Medicine, Chicago, IL, United StatesIntroductionResponses to allogeneic human leukocyte antigen (HLA) molecules limit the survival of transplanted organs. The changes in T-cell alloreactivity that contribute to this process, however, are not fully understood. We defined a set of donor reactive T-cell clones (DRTC) with the goal to elucidate signatures of kidney allograft rejection.MethodsDRTC were identified pretransplant using an anti-donor mixed lymphocyte reaction assay: CFSE-diluting CD4+ and CD8+ DRTC were flow-sorted, and the TCR sequences were identified using Adaptive Immunosequencing. DRTC were then tracked in post-transplant biopsies, blood, and urine samples in a cohort of kidney transplant recipients.ResultsIn patients with an abnormal biopsy, the majority of CD8+ DRTC found within the allograft were detected in the circulating pre-transplant repertoire. Circulating CD8+ DRTC were more abundant pre- and post-transplant in patients that received non-lymphodepletional induction and developed an abnormal biopsy when compared to stable patients. Additionally, DRTC were detected as early as two weeks post-transplant in the urine of some patients, with some of these clones subsequently identified in follow-up kidney biopsy samples.DiscussionThe findings of our study add to our understanding of T-cell alloreactivity following kidney transplantation and provide evidence for the role of pre-defined alloreactive T-cells in the development of allograft rejection.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1516772/fullkidney transplant rejectionalloreactivityT-cell receptor sequencingT-cell mediated rejectionmechanisms of rejection |
| spellingShingle | Jes M. Sanders Barbara L. Banbury Erika L. Schumacher Jie He Yuvaraj Sambandam Paul A. Fields Lorenzo Gallon Lorenzo Gallon James M. Mathew James M. Mathew James M. Mathew Joseph R. Leventhal Joseph R. Leventhal Pre-transplant T-cell clonal analysis identifies CD8+ donor reactive clones that contribute to kidney transplant rejection Frontiers in Immunology kidney transplant rejection alloreactivity T-cell receptor sequencing T-cell mediated rejection mechanisms of rejection |
| title | Pre-transplant T-cell clonal analysis identifies CD8+ donor reactive clones that contribute to kidney transplant rejection |
| title_full | Pre-transplant T-cell clonal analysis identifies CD8+ donor reactive clones that contribute to kidney transplant rejection |
| title_fullStr | Pre-transplant T-cell clonal analysis identifies CD8+ donor reactive clones that contribute to kidney transplant rejection |
| title_full_unstemmed | Pre-transplant T-cell clonal analysis identifies CD8+ donor reactive clones that contribute to kidney transplant rejection |
| title_short | Pre-transplant T-cell clonal analysis identifies CD8+ donor reactive clones that contribute to kidney transplant rejection |
| title_sort | pre transplant t cell clonal analysis identifies cd8 donor reactive clones that contribute to kidney transplant rejection |
| topic | kidney transplant rejection alloreactivity T-cell receptor sequencing T-cell mediated rejection mechanisms of rejection |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1516772/full |
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