ArticleProceedings of the National Academy of Sciences of the United States of America2014
Impaired selectin-dependent leukocyte recruitment induces T-cell exhaustion and prevents chronic allograft vasculopathy and rejection.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- An Emerging Role of TIM3 Expression on T Cells in Chronic Kidney Inflammation.Frontiers in immunology · 2021Pooled it
- Neuropilin-2 functions as a coinhibitory receptor to regulate antigen-induced inflammation and allograft rejection.The Journal of clinical investigation · 2025Article
- Identification of novel germline mutations in FUT7 and EXT1 linked with hereditary multiple exostoses.Oncogene · 2025Article
- T Cell Exhaustion in Allergic Diseases and Allergen Immunotherapy: A Novel Biomarker?Current allergy and asthma reports · 2025Review
- Exhaustion of T cells after renal transplantation.Frontiers in immunology · 2024Review
- Immune Checkpoints in Solid Organ Transplantation.Biology · 2023Review
- Reduced Satb1 expression predisposes CD4Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The CD226/TIGIT axis is involved in T cell hypo-responsiveness appearance in long-term kidney transplant recipients.Scientific reports · 2022Article
- CD4 T-Cell Exhaustion: Does It Exist and What Are Its Roles in Cancer?Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Review
- miR-21 antagonism reprograms macrophage metabolism and abrogates chronic allograft vasculopathy.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2021Article
- Article
- Coupling of Co-expression Network Analysis and Machine Learning Validation Unearthed Potential Key Genes Involved in Rheumatoid Arthritis.Frontiers in genetics · 2021Article
- T cell reconstitution after lymphocyte depletion features a different pattern of inhibitory receptor expression in ABO- versus HLA-incompatible kidney transplant recipients.Clinical and experimental immunology · 2020Article
- Diet-induced obesity exacerbates imiquimod-mediated psoriasiform dermatitis in anti-PD-1 antibody-treated mice: Implications for patients being treated with checkpoint inhibitors for cancer.Journal of dermatological science · 2020Article
- Resilience of T cell-intrinsic dysfunction in transplantation tolerance.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Impact of infection on transplantation tolerance.Immunological reviews · 2019Review
- T-cell exhaustion correlates with improved outcomes in kidney transplant recipients.Kidney international · 2019Observational
- The pursuit of transplantation tolerance: new mechanistic insights.Cellular & molecular immunology · 2019Article
- Exhausted and Senescent T Cells at the Maternal-Fetal Interface in Preterm and Term Labor.Journal of immunology research · 2019Article
- T cell Allorecognition Pathways in Solid Organ Transplantation.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 3 countries.
Funding
Abstract
Selectin-selectin ligand interactions mediate the initial steps in leukocyte migration, an integral part of immune responses. Fucosyltransferase-VII (FucT-VII), encoded by Fut7, is essential for biosynthesis of selectin ligands. In an established model of cardiac allograft vasculopathy and chronic rejection, Fut7(-/-) recipients exhibited long-term graft survival with minimal vasculopathy compared with WT controls. Graft survival was associated with CD4 T-cell exhaustion in the periphery, characterized by impaired effector cytokine production, defective proliferation, increased expression of inhibitory receptors programmed death-1 (PD-1) and T cell Ig- and mucin-domain-containing molecule-3 (Tim-3), low levels of IL-7Rα on CD4 T cells, and reduced migration of polyfunctional CD4 memory T cells to the allograft. Blocking PD-1 triggered rejection only in Fut7(-/-) recipients, whereas depleting regulatory T cells had no effect in either Fut7(-/-) or WT recipients. Adoptive transfer experiments confirmed that this CD4 T cell-exhausted phenotype is seen primarily in Fut7(-/-) CD4 T cells. These data suggest that impaired leukocyte recruitment is a novel mechanism leading to CD4 T-cell exhaustion. Our experimental system serves as an excellent model to study CD4 T-cell exhaustion as a dominant mechanism of transplant tolerance. Further, targeting FucT-VII may serve as a promising strategy to prevent chronic allograft rejection and promote tolerance.
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Registered trials
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