ArticleFrontiers in immunology2021
Expression of Senescence Marker TIGIT Identifies Polyfunctional Donor-Reactive CD4+ T Cells Preferentially Lost After Kidney Transplantation.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 25 citations in OpenAlex.
- Tacrolimus Monotherapy is Safe in Immunologically Low-Risk Kidney Transplant Recipients: A Randomized-Controlled Pilot Study.Transplant international : official journal of the European Society for Organ Transplantation · 2022Trial
- Therapeutic Immune Reprogramming by Rapamycin Attenuates Plaque Inflammation and Lymphoid Immune Responses in Aged Atherosclerotic Mice.Aging cell · 2026Article
- TIGITFrontiers in immunology · 2026Review
- Immunosenescence accelerates atherosclerosis development in AAV-PCSK9 mouse model.GeroScience · 2025Article
- Engineered CD4 TCR T cells with conserved high-affinity TCRs targeting NY-ESO-1 for advanced cellular therapies in cancer.Science advances · 2025Article
- Differential susceptibility and role for senescence in CART cells based on costimulatory domains.Molecular cancer · 2025Article
- CD4 T cell dysfunction is associated with bacterial recrudescence during chronic tuberculosis.Nature communications · 2025Article
- CD4 T cell dysfunction is associated with bacterial recrudescence during chronic tuberculosis.bioRxiv : the preprint server for biology · 2025Article
- The perioperative management of geriatric patients in transplantation surgery-clinical, immunological, and translational considerations.Frontiers in transplantation · 2025Review
- T cell Activation Marker HLA-DR Reflects Tacrolimus-Associated Immunosuppressive Burden and BK Viremia Risk After Kidney Transplantation - An Observational Cohort Study.Transplant international : official journal of the European Society for Organ Transplantation · 2025Observational
- Exhaustion of T cells after renal transplantation.Frontiers in immunology · 2024Review
- Older age is associated with a distinct and marked reduction of functionality of both alloreactive CD4+ and CD8+ T cells.Frontiers in immunology · 2024Article
- TIGIT regulates CD4Frontiers in immunology · 2024Article
- Immune Checkpoints in Solid Organ Transplantation.Biology · 2023Review
- Polyfunctional donor-reactive T cells are associated with acute T-cell-mediated rejection of the kidney transplant.Clinical and experimental immunology · 2023Article
- Single-Cell RNA Sequencing of Donor-Reactive T Cells Reveals Role of Apoptosis in Donor-Specific Hyporesponsiveness of Kidney Transplant Recipients.International journal of molecular sciences · 2023Article
- Lowering maintenance immune suppression in elderly kidney transplant recipients; connecting the immunological and clinical dots.Frontiers in medicine · 2023Review
- The Incidence of Antibody-Mediated Rejection Is Age-Related, Plateaus Late After Kidney Transplantation, and Contributes Little to Graft Loss in the Older Recipients.Transplant international : official journal of the European Society for Organ Transplantation · 2023Article
- TIGIT as a Promising Therapeutic Target in Autoimmune Diseases.Frontiers in immunology · 2022Review
- Transcriptomic analysis of graft liver provides insight into the immune response of rat liver transplantation.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Development of T-cell hyporesponsiveness to donor antigen may explain the substantial decreased risk for acute rejection in the years following kidney transplantation. The underlying mechanisms of donor-specific hyporesponsiveness (DSH) are largely unknown but may allow for lowering of immunosuppressive medication. Due to the onset of DSH being more rapid and pronounced in older recipients (+55 years), we hypothesized that immunosenescence/exhaustion of T lymphocytes would be a contributing factor. This study tested whether donor-reactive recipient T cells become hyporesponsive due to exhaustion from continuous stimulation by donor antigen. Circulating donor-reactive T cells of both young and elderly stable kidney transplant recipients (N=17) before and 3-5 years after transplantation were analyzed at the single cell level for expression of exhaustion markers by multi-parameter flow cytometry followed by unsupervised and unbiased clustering. Clusters containing cells of a particular expression profile with significant differential abundance after transplantation were identified and further analyzed. Unexpectedly, our results do not demonstrate an increase in exhausted donor antigen-reactive T cells post transplantation. Instead, we demonstrate a significant decrease in donor antigen-reactive CD4+ T cells expressing T cell immunoglobulin and ITIM domain (TIGIT) long after transplantation. Further analysis at earlier timepoints indicated that this decrease is already present at six months post transplantation. Characterization of these CD4+ T donor-reactive cells expressing TIGIT revealed them to have a predominantly central and effector memory T cell phenotype and a highly poly-functional cytokine expression profile. This study has therefore identified TIGIT as a marker for a previously undescribed polyfunctional donor-reactive CD4+ T cell population whose decline following kidney transplantation may explain development of DSH.
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