ArticleProceedings of the National Academy of Sciences of the United States of America2015
CD8 T-cell recognition of acquired alloantigen promotes acute allograft rejection.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 108 citations in OpenAlex.
- Advances in HLA and Non-HLA Immune Profiling: Integrating Next-Generation Sequencing and Artificial Intelligence in Transplantation.Annals of laboratory medicine · 2026Review
- Genome-edited safe and immune-evasive human pluripotent cells: Potential solution for allogeneic therapies.Stem cell reports · 2026Article
- Autologous immune system reset for kidney allograft acceptance: mechanisms, evidence, and a testable reconstitution-window model.Frontiers in medicine · 2026Review
- Early considerations for village-in-a-dish platform: a multidisciplinary perspective.Frontiers in bioengineering and biotechnology · 2026Review
- The Myeloid-T Lymphocyte Axis in Chronic Lung Allograft Rejection: Emerging Insights into the Immune Circuitry Driving Fibrosis.Results and problems in cell differentiation · 2026Review
- Regulatory dendritic cells and their usefulness in mitigating solid organ transplant rejection.Clinical transplantation and research · 2025Review
- Intestinal reengineering: Scientific advances in intestinal transplantation.World journal of gastrointestinal surgery · 2025Review
- Quantitative and large-scale investigation of human TCR-HLA cross-reactivity.Science advances · 2025Article
- Selective agonists of KIR and NKG2A to evade missing self response of natural killer cells.Scientific reports · 2025Article
- Lung adenocarcinoma-derived IFN-γ promotes growth by modulating CD8+ T cell production of CCR5 chemokines.The Journal of clinical investigation · 2025Article
- Unraveling CD8American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025Review
- Discovering molecular signatures in kidney transplant biopsies with borderline changes and isolated V-lesions: single-cell RNA-sequencing analysis of human blood and tissue Spatial transcriptomics.Scientific reports · 2025Article
- Extracellular Vesicles and Immune Activation in Solid Organ Transplantation: The Impact of Immunosuppression.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Graft-derived extracellular vesicles transport miRNAs to modulate macrophage polarization after heart transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025Article
- Adenosine triphosphate-mediated signaling of P2X7 receptors controls donor extracellular vesicle release and major histocompatibility complex cross-decoration after allotransplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025Article
- The effects of interleukin-21 in the biology of transplant rejection.Frontiers in immunology · 2025Review
- Targeting T helper 17 cells: emerging strategies for overcoming transplant rejection.Clinical transplantation and research · 2024Review
- Mechanisms of allorecognition and xenorecognition in transplantation.Clinical transplantation and research · 2024Review
- B2M or CIITA knockdown decreased the alloimmune response of dental pulp stem cells: an in vitro study.Stem cell research & therapy · 2024Article
- Evaluating Interleukin-2 and Its Receptors As Indicators of Acute Renal Graft Rejection.Cureus · 2024Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Adaptive CD8 T-cell immunity is the principal arm of the cellular alloimmune response, but its development requires help. This can be provided by CD4 T cells that recognize alloantigen "indirectly," as self-restricted allopeptide, but this process remains unexplained, because the target epitopes for CD4 and CD8 T-cell recognition are "unlinked" on different cells (recipient and donor antigen presenting cells (APCs), respectively). Here, we test the hypothesis that the presentation of intact and processed MHC class I alloantigen by recipient dendritic cells (DCs) (the "semidirect" pathway) allows linked help to be delivered by indirect-pathway CD4 T cells for generating destructive cytotoxic CD8 T-cell alloresponses. We show that CD8 T-cell-mediated rejection of murine heart allografts that lack hematopoietic APCs requires host secondary lymphoid tissue (SLT). SLT is necessary because within it, recipient dendritic cells can acquire MHC from graft parenchymal cells and simultaneously present it as intact protein to alloreactive CD8 T cells and as processed peptide alloantigen for recognition by indirect-pathway CD4 T cells. This enables delivery of essential help for generating cytotoxic CD8 T-cell responses that cause rapid allograft rejection. In demonstrating the functional relevance of the semidirect pathway to transplant rejection, our findings provide a solution to a long-standing conundrum as to why SLT is required for CD8 T-cell allorecognition of graft parenchymal cells and suggest a mechanism by which indirect-pathway CD4 T cells provide help for generating effector cytotoxic CD8 T-cell alloresponses at late time points after transplantation.
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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.