ArticleJournal of immunology (Baltimore, Md. : 1950)2009
Dominant role of antigen dose in CD4+Foxp3+ regulatory T cell induction and expansion.
Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
110 citing papers in PubMed, 173 citations in OpenAlex.
- HnRNP L is essential for peripheral T cell proliferation and survival.Frontiers in immunology · 2025Article
- Lipid-Polymer Hybrid Nanoparticles Utilize B Cells and Dendritic Cells to Elicit Distinct Antigen-Specific CD4ACS applied bio materials · 2024Review
- Deciphering the role of protein kinase A in the control of FoxP3 expression in regulatory T cells in health and autoimmunity.Scientific reports · 2024Article
- The regulation and differentiation of regulatory T cells and their dysfunction in autoimmune diseases.Nature reviews. Immunology · 2024Review
- Phosphorylation of hnRNP A1-Serine 199 Is Not Required for T Cell Differentiation and Function.ImmunoHorizons · 2024Article
- Combined Treatment With TGF-β1, Retinoic Acid, and Lactoferrin Robustly Generate Inducible Tregs (iTregs) Against High Affinity Ligand.Immune network · 2023Article
- Immunoregulation: the interplay between metabolism and redox homeostasis.Frontiers in transplantation · 2023Review
- Recent insights into the role of Akt in CD4 T-cell activation and differentiation: alternative splicing and beyond.Immunometabolism (Cobham, Surrey) · 2023Review
- Droplet Microfluidic Technology for the Early and Label-Free Isolation of Highly-Glycolytic, Activated T-Cells.Micromachines · 2022Article
- Research Progress on the Immunogenicity and Regeneration of Acellular Adipose Matrix: A Mini Review.Frontiers in bioengineering and biotechnology · 2022Review
- In Vivo Expansion of Antigen-Specific Regulatory T Cells through Staggered Fc.IL-2 Mutein Dosing and Antigen-Specific Immunotherapy.ImmunoHorizons · 2021Article
- CAR- and TRuC-redirected regulatory T cells differ in capacity to control adaptive immunity to FVIII.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Methoxy polyethylene glycol modification promotes adipogenesis by inducing the production of regulatory T cells in xenogeneic acellular adipose matrix.Materials today. Bio · 2021Article
- Kynurenines as a Novel Target for the Treatment of Malignancies.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Strength and Numbers: The Role of Affinity and Avidity in the 'Quality' of T Cell Tolerance.Cells · 2021Review
- Hyaluronan synthesis inhibition impairs antigen presentation and delays transplantation rejection.Matrix biology : journal of the International Society for Matrix Biology · 2021Article
- Crosstalk of Microorganisms and Immune Responses in Autoimmune Neuroinflammation: A Focus on Regulatory T Cells.Frontiers in immunology · 2021Review
- Diverse Roles of Akt in T cells.Immunometabolism · 2021Article
- Hepatitis B envelope antigen increases Tregs by converting CD4+CD25Experimental and therapeutic medicine · 2020Article
- Lactoferrin Induces Tolerogenic Bone Marrow-Derived Dendritic Cells.Immune network · 2020Article
50 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The definitions of tolerogenic vs immunogenic dendritic cells (DC) remain controversial. Immature DC have been shown to induce T regulatory cells (Treg) specific for foreign and allogeneic Ags. However, we have previously reported that mature DC (mDC) prevented the onset of autoimmune diabetes, whereas immature DC (iDC) were therapeutically ineffective. In this study, islet-specific CD4(+) T cells from BDC2.5 TCR-transgenic mice were stimulated in the absence of exogenous cytokine with iDC or mDC pulsed with high- or low-affinity antigenic peptides and examined for Treg induction. Both iDC and mDC presenting low peptide doses induced weak TCR signaling via the Akt/mammalian target of rapamycin (mTOR) pathway, resulting in significant expansion of Foxp3(+) Treg. Furthermore, unpulsed mDC, but not iDC, also induced Treg. High peptide doses induced strong Akt/mTOR signaling and favored the expansion of Foxp3(neg) Th cells. The inverse correlation of Foxp3 and Akt/mTOR signaling was also observed in DO11.10 and OT-II TCR-transgenic T cells and was recapitulated with anti-CD3/CD28 stimulation in the absence of DC. IL-6 production in these cultures correlated positively with Ag dose and inversely with Treg expansion. Studies with T cells or DC from IL-6(-/-) mice revealed that IL-6 production by T cells was more important in the inhibition of Treg induction at low Ag doses. These studies indicate that the strength of Akt/mTOR signaling, a critical T cell-intrinsic determinant for Treg vs Th induction, can be controlled by adjusting the dose of antigenic peptide. Furthermore, this operates in a dominant fashion over DC phenotype and cytokine production.
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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.