ArticleJournal of immunology (Baltimore, Md. : 1950)2011
Tolerance induced by apoptotic antigen-coupled leukocytes is induced by PD-L1+ and IL-10-producing splenic macrophages and maintained by T regulatory cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers.
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Who cites it
134 citing papers in PubMed.
- TAK-101 Nanoparticles Induce Gluten-Specific Tolerance in Celiac Disease: A Randomized, Double-Blind, Placebo-Controlled Study.Gastroenterology · 2021Trial
- Kupffer cells are key mediators of antigen-specific immune tolerance by peptide-coupled red blood cells.Science advances · 2026Article
- Poly(lactic-co-glycolic acid) immunomodulatory nanoparticles attenuate neuroinflammation and Alzheimer's disease-related pathology in 5xFAD mice.bioRxiv : the preprint server for biology · 2026Article
- Erythrocyte-antibody conjugates to overcome immunotherapy resistance.Nature cancer · 2026Article
- Erythrocyte-anti-PD1 conjugates in persons with advanced solid tumors resistant to anti-PD1/PDL1: preclinical characterization and results of a phase 1 trial.Nature cancer · 2026Article
- Allospecific splenic Tr1 cells drive effector T cell exhaustion through up-regulated Areg-EGFR signaling to promote transplant tolerance.Science advances · 2026Article
- STING/type I interferon pathway is required for antigen-containing PLGA nanoparticle- and apoptotic cell-induced CD4+ T cell tolerance.Science advances · 2026Article
- Reprogramming autoimmunity: inducing antigen-specific tolerance via apoptotic mimicry in an experimental model of multiple sclerosis.Journal of neuroinflammation · 2025Article
- Multiple sclerosis: molecular pathogenesis and therapeutic intervention.Signal transduction and targeted therapy · 2025Review
- Fate and long-lasting therapeutic effects of mesenchymal stromal/stem-like cells: mechanistic insights.Stem cell research & therapy · 2025Review
- Unlocking Transplant Tolerance with Biomaterials.Advanced healthcare materials · 2025Review
- Microparticles incorporating dual apoptotic factors to inhibit inflammatory effects in macrophages.Journal of pharmaceutical sciences · 2024Article
- Developing an erythrocyte‒MHC-I conjugate for cancer treatment.Cell discovery · 2024Article
- Hydrogel-based approaches to target hypersensitivity mechanisms underlying autoimmune disease.Advanced drug delivery reviews · 2024Review
- Biomaterial-enhanced treg cell immunotherapy: A promising approach for transplant medicine and autoimmune disease treatment.Bioactive materials · 2024Review
- Article
- Cutting edge of immune response and immunosuppressants in allogeneic and xenogeneic islet transplantation.Frontiers in immunology · 2024Review
- Immunomodulatory nano-preparations for rheumatoid arthritis.Drug delivery · 2023Review
- Cell and biomaterial delivery strategies to induce immune tolerance.Advanced drug delivery reviews · 2023Review
- Nanoparticle dose and antigen loading attenuate antigen-specific T-cell responses.Biotechnology and bioengineering · 2023Article
74 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Ag-specific tolerance is a highly desired therapy for immune-mediated diseases. Intravenous infusion of protein/peptide Ags linked to syngeneic splenic leukocytes with ethylene carbodiimide (Ag-coupled splenocytes [Ag-SP]) has been demonstrated to be a highly efficient method for inducing peripheral, Ag-specific T cell tolerance for treatment of autoimmune disease. However, little is understood about the mechanisms underlying this therapy. In this study, we show that apoptotic Ag-SP accumulate in the splenic marginal zone, where their uptake by F4/80(+) macrophages induces production of IL-10, which upregulates the expression of the immunomodulatory costimulatory molecule PD-L1 that is essential for Ag-SP tolerance induction. Ag-SP infusion also induces T regulatory cells that are dispensable for tolerance induction but required for long-term tolerance maintenance. Collectively, these results indicate that Ag-SP tolerance recapitulates how tolerance is normally maintained in the hematopoietic compartment and highlight the interplay between the innate and adaptive immune systems in the induction of Ag-SP tolerance. To our knowledge, we show for the first time that tolerance results from the synergistic effects of two distinct mechanisms, PD-L1-dependent T cell-intrinsic unresponsiveness and the activation of T regulatory cells. These findings are particularly relevant as this tolerance protocol is currently being tested in a Phase I/IIa clinical trial in new-onset relapsing-remitting multiple sclerosis.
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Registered trials
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