ArticleJournal of immunology (Baltimore, Md. : 1950)2006
TLR agonists abrogate costimulation blockade-induced prolongation of skin allografts.
Article in Journal of immunology (Baltimore, Md. : 1950), 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 127 citations in OpenAlex.
- The Fas-FasL system: from apoptosis regulator to therapeutic target in autoimmunity, cancer, and transplantation.Immunologic research · 2026Review
- The inhibitory receptor Siglec-E controls antigen-presenting cell activation and T cell-mediated transplant rejection.Science translational medicine · 2025Article
- T cell responsiveness to IL-10 defines the immunomodulatory effect of costimulation blockade via anti-CD154 and impacts transplant survival.bioRxiv : the preprint server for biology · 2024Article
- Mechanisms governing bystander activation of T cells.Frontiers in immunology · 2024Review
- Sex as a biological variable: Mechanistic insights and clinical relevance in solid organ transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2023Review
- Methods to Study TLRs in Transplantation.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Recent advances into the role of pattern recognition receptors in transplantation.Cellular immunology · 2020Review
- Trained immunity in organ transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2020Review
- Diverse Routes of Allograft Tolerance Disruption by Memory T Cells.Frontiers in immunology · 2020Review
- Cutting Edge: Early Attrition of Memory T Cells during Inflammation and Costimulation Blockade Is Regulated Concurrently by Proapoptotic Proteins Fas and Bim.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Murine CMV induces type 1 IFN that impairs differentiation of MDSCs critical for transplantation tolerance.Blood advances · 2018Article
- Murine models of transplantation tolerance through mixed chimerism: advances and roadblocks.Clinical and experimental immunology · 2017Review
- Infectious pathogens may trigger specific allo-HLA reactivity via multiple mechanisms.Immunogenetics · 2017Review
- Disruption of Transplant Tolerance by an "Incognito" Form of CD8 T Cell-Dependent Memory.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2017Article
- TLR-Induced Murine Dendritic Cell (DC) Activation Requires DC-Intrinsic Complement.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Danger signals in regulating the immune response to solid organ transplantation.The Journal of clinical investigation · 2017Review
- Regulatory T cell expressed MyD88 is critical for prolongation of allograft survival.Transplant international : official journal of the European Society for Organ Transplantation · 2016Article
- Innate immune mechanisms in transplant allograft vasculopathy.Current opinion in organ transplantation · 2016Review
- Contrasting Roles of Islet Resident Immunoregulatory Macrophages and Dendritic Cells in Experimental Autoimmune Type 1 Diabetes.PloS one · 2016Article
- Innate allorecognition.Immunological reviews · 2014Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Costimulation blockade protocols are effective in prolonging allograft survival in animal models and are entering clinical trials, but how environmental perturbants affect graft survival remains largely unstudied. We used a costimulation blockade protocol consisting of a donor-specific transfusion and anti-CD154 mAb to address this question. We observed that lymphocytic choriomeningitis virus infection at the time of donor-specific transfusion and anti-CD154 mAb shortens allograft survival. Lymphocytic choriomeningitis virus 1) activates innate immunity, 2) induces allo-cross-reactive T cells, and 3) generates virus-specific responses, all of which may adversely affect allograft survival. To investigate the role of innate immunity, mice given costimulation blockade and skin allografts were coinjected with TLR2 (Pam3Cys), TLR3 (polyinosinic:polycytidylic acid), TLR4 (LPS), or TLR9 (CpG) agonists. Costimulation blockade prolonged skin allograft survival that was shortened after coinjection by TLR agonists. To investigate underlying mechanisms, we used "synchimeric" mice which circulate trace populations of anti-H2b transgenic alloreactive CD8+ T cells. In synchimeric mice treated with costimulation blockade, coadministration of all four TLR agonists prevented deletion of alloreactive CD8+ T cells and shortened skin allograft survival. These alloreactive CD8+ T cells 1) expressed the proliferation marker Ki-67, 2) up-regulated CD44, and 3) failed to undergo apoptosis. B6.TNFR2-/- and B6.IL-12R-/- mice treated with costimulation blockade plus LPS also exhibited short skin allograft survival whereas similarly treated B6.CD8alpha-/- and TLR4-/- mice exhibited prolonged allograft survival. We conclude that TLR signaling abrogates the effects of costimulation blockade by preventing alloreactive CD8+ T cell apoptosis through a mechanism not dependent on TNFR2 or IL-12R signaling.
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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.