ArticleJournal of the American Society of Nephrology : JASN2016
Memory CD4 T Cells Induce Antibody-Mediated Rejection of Renal Allografts.
Article in Journal of the American Society of Nephrology : JASN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 50 citations in OpenAlex.
- Elevated number of IL-21+ TFH and CD86+CD38+ B cells in blood of renal transplant recipients with AMR under conventional immuno-suppression.International journal of immunopathology and pharmacologyTrial
- LAG3 regulates antibody responses in a murine model of kidney transplantation.The Journal of clinical investigation · 2025Article
- Can mouse kidney transplant models inform mechanisms of injury and acceptance in clinical kidney transplantation?American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025Review
- Donor-specific antibodies against HLA-C, HLA-DP and HLA-DQ and their implications in kidney transplantation.World journal of transplantation · 2025Review
- Article
- Marginal zone B cells are required for optimal humoral responses to allograft.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025Article
- Activation and Regulation of Indirect Alloresponses in Transplanted Patients With Donor Specific Antibodies and Chronic Rejection.Transplant international : official journal of the European Society for Organ Transplantation · 2024Review
- Pretransplant, Th17 dominant alloreactivity in highly sensitized kidney transplant candidates.Frontiers in transplantation · 2024Article
- Autoantibodies against DNA topoisomerase I promote renal allograft rejection by increasing alloreactive T cell responses.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2023Article
- The IMBG Test for Evaluating the Pharmacodynamic Response to Immunosuppressive Therapy in Kidney Transplant Patients: Current Evidence and Future Applications.International journal of molecular sciences · 2023Article
- Beyond the thrombus: Platelet-inspired nanomedicine approaches in inflammation, immune response, and cancer.Journal of thrombosis and haemostasis : JTH · 2022Review
- The Ratio of CD226 and TIGIT Expression in Tfh and PD-1Journal of immunology research · 2022Article
- Clinical Case: Patient with Mixed Graft Rejection Four Days after Kidney Transplantation Developed Specific Antibodies against Donor Bw4 Specificities.Antibodies (Basel, Switzerland) · 2021Article
- T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation.Frontiers in immunology · 2021Article
- Clinical Significance of Shared T Cell Epitope Analysis in EarlyFrontiers in immunology · 2021Article
- Expression of Senescence Marker TIGIT Identifies Polyfunctional Donor-Reactive CD4+ T Cells Preferentially Lost After Kidney Transplantation.Frontiers in immunology · 2021Article
- Memory T Cells in Transplantation: Old Challenges Define New Directions.Transplantation · 2020Review
- Early T cell infiltration is modulated by programed cell death-1 protein and its ligand (PD-1/PD-L1) interactions in murine kidney transplants.Kidney international · 2020Article
- Role of novel biomarkers in kidney transplantation.World journal of transplantation · 2020Review
- Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction.International journal of molecular sciences · 2020Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Despite advances in immunosuppression, antibody-mediated rejection is a serious threat to allograft survival. Alloreactive memory helper T cells can induce potent alloantibody responses and often associate with poor graft outcome. Nevertheless, the ability of memory T cells to elicit well characterized manifestations of antibody-mediated rejection has not been tested. We investigated helper functions of memory CD4 T cells in a mouse model of renal transplantation. Whereas the majority of unsensitized C57Bl/6 recipients spontaneously accepted fully MHC-mismatched A/J renal allografts, recipients containing donor-reactive memory CD4 T cells rapidly lost allograft function. Increased serum creatinine levels, high serum titers of donor-specific alloantibody, minimal T cell infiltration, and intense C4d deposition in the grafts of sensitized recipients fulfilled all diagnostic criteria for acute renal antibody-mediated rejection in humans. IFNγ neutralization did not prevent the renal allograft rejection induced by memory helper T cells, and CD8 T cell depletion at the time of transplantation or depletion of both CD4 and CD8 T cells also did not prevent the renal allograft rejection induced by memory helper T cells starting at day 4 after transplantation. However, B cell depletion inhibited alloantibody generation and significantly extended allograft survival, indicating that donor-specific alloantibodies (not T cells) were the critical effector mechanism of renal allograft rejection induced by memory CD4 T cells. Our studies provide direct evidence that recipient T cell sensitization may result in antibody-mediated rejection of renal allografts and introduce a physiologically relevant animal model with which to investigate mechanisms of antibody-mediated rejection and novel therapeutic approaches for its prevention and treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.