ArticleThe Journal of clinical investigation2024
Dysfunction of infiltrating cytotoxic CD8+ T cells within the graft promotes murine kidney allotransplant tolerance.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Once yearly cell-based therapy for sustained and dose-tunable delivery of monoclonal antibodies.Science advances · 2026Article
- T-Cell Remodeling in Renal Fibrosis: From Acute Injury to Chronic Kidney Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Single Cell Multi-Omics Revealing the Important Role of MR1 Mediated MAIT Cells in Maintaining Rejection for Liver Transplantation.Cell proliferation · 2026Article
- IL-2 mutein promotes antigen-specific transplant acceptance in mice through expansion of ST2Nature communications · 2026Article
- CD8Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Tissue-resident memory T cells in organ transplantation: implications for immune homeostasis and graft outcomes.Inflammation and regeneration · 2026Review
- NaCl and urea modulate CD8+ T cell survival, renal accumulation, and response to BK virus.JCI insight · 2025Article
- The roles of tertiary lymphoid structures in orchestrating immune responses in peripheral organs.Inflammation and regeneration · 2025Review
- Review
- Defensive tolerance drives the reprogramming and dysfunction of infiltrating pathogenic B cells assuring the maintenance of tolerance.Research square · 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
- Maintenance of graft tissue-resident Foxp3+ cells is necessary for lung transplant tolerance in mice.The Journal of clinical investigation · 2025Article
- Identification and characterization of senescent macrophages in renal allograft rejection: a cross-species MultiOmics study.Frontiers in immunology · 2025Article
- What makes the kidney so tolerant?The Journal of clinical investigation · 2024Article
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Tolerance of mouse kidney allografts arises in grafts that develop regulatory tertiary lymphoid organs (rTLOs). Single-cell RNA-seq (scRNA-seq) data and adoptive transfer of alloreactive T cells after transplantation showed that cytotoxic CD8+ T cells are reprogrammed within the accepted graft to an exhausted/regulatory-like phenotype mediated by IFN-γ. Establishment of rTLOs was required because adoptive transfer of alloreactive T cells prior to transplantation results in kidney allograft rejection. Despite the presence of intragraft CD8+ cells with a regulatory phenotype, they were not essential for the induction and maintenance of kidney allograft tolerance since renal allotransplantation into CD8-KO recipients resulted in acceptance and not rejection. Analysis of scRNA-seq data from allograft kidneys and malignant tumors identified similar regulatory-like cell types within the T cell clusters and trajectory analysis showed that cytotoxic CD8+ T cells are reprogrammed into an exhausted/regulatory-like phenotype intratumorally. Induction of cytotoxic CD8+ T cell dysfunction of infiltrating cells appears to be a beneficial mechanistic pathway that protects the kidney allotransplant from rejection through a process we call "defensive tolerance." This pathway has implications for our understanding of allotransplant tolerance and tumor resistance to host immunity.
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