ArticleDiabetologia2014
Low TCR signal strength induces combined expansion of Th2 and regulatory T cell populations that protect mice from the development of type 1 diabetes.
Article in Diabetologia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 24 citations in OpenAlex.
- Regulatory T cells in autoimmune diseases: biological mechanisms, clinical translation, and translational challenges.Frontiers in immunology · 2026Review
- HnRNP L is essential for peripheral T cell proliferation and survival.Frontiers in immunology · 2025Article
- Phosphorylation of hnRNP A1-Serine 199 Is Not Required for T Cell Differentiation and Function.ImmunoHorizons · 2024Article
- The Biological Significance of Trogocytosis.Results and problems in cell differentiation · 2024Article
- Th2 cell clonal expansion at diagnosis in human type 1 diabetes.Clinical immunology (Orlando, Fla.) · 2023Article
- Jiang Zhi Granule protects immunological barrier of intestinal mucosa in rats with non-alcoholic steatohepatitis.Pharmaceutical biology · 2021Article
- Lymphocytes and Trogocytosis-Mediated Signaling.Cells · 2021Review
- Cutting Edge: Tissue Antigen Expression Levels Fine-Tune T Cell Differentiation Decisions In Vivo.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- MHCII-restricted T helper cells: an emerging trigger for chronic tactile allodynia after nerve injuries.Journal of neuroinflammation · 2020Review
- Trogocytosis-Mediated Intracellular Signaling in CD4Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- T cells transduce T-cell receptor signal strength by generating different phosphatidylinositols.The Journal of biological chemistry · 2019Article
- Differential T-cell receptor signals for T helper cell programming.Immunology · 2018Review
- Altered Function of Antigen-Presenting Cells in Type 1 Diabetes: A Challenge for Antigen-Specific Immunotherapy?Diabetes · 2018Review
- CTLA‑4 interferes with the HBV‑specific T cell immune response (Review).International journal of molecular medicine · 2018Review
- Metabolic pressure and the breach of immunological self-tolerance.Nature immunology · 2017Article
- PKC-ѳ is dispensable for OX40L-induced TCR-independent Treg proliferation but contributes by enabling IL-2 production from effector T-cells.Scientific reports · 2017Article
- TCR Signal Strength Regulates Akt Substrate Specificity To Induce Alternate Murine Th and T Regulatory Cell Differentiation Programs.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Unique Features of Pancreatic-Resident Regulatory T Cells in Autoimmune Type 1 Diabetes.Frontiers in immunology · 2017Review
- Cutting Edge: Differential Regulation of PTEN by TCR, Akt, and FoxO1 Controls CD4+ T Cell Fate Decisions.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Modeling the T cell immune response: a fascinating challenge.Journal of pharmacokinetics and pharmacodynamics · 2014Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
aims/hypothesisWeak stimulation of CD4(+) T cells induces expansion of CD4(+) forkhead box P3(+) regulatory T cells (Tregs) and can also promote T helper (Th) 2 responses, which have demonstrable beneficial effects on autoimmune diabetes. This study explored the feasibility of combined Treg/Th2 expansion for immunotherapy of type 1 diabetes in NOD mice.
methodsWe compared Treg and Th responses to dendritic cells (DC) presenting scaled antigen doses to islet-specific NOD CD4(+) T cells. Flow cytometric and Luminex analyses were performed to determine the phenotype and cytokine profile of expanded T cells. The ability of expanded T cells to prevent type 1 diabetes was tested in an adoptive transfer model.
resultsIn vitro studies revealed a hierarchical, selective expansion of Treg and T effector (Teff) populations at different antigen doses. Thus, a single low dose produced a mixture of Tregs Th2 and type 1 regulatory (Tr1) cells, which prevented diabetes in NOD-SCID mice and increased the ratio of Treg/Teff cells infiltrating the pancreatic islets. Subcutaneous injection of DC, previously shown to prevent diabetes in NOD mice, induced expansion of the same mixture of Tregs Tr1 and Th2 cells. Low-dose expansion of Treg required MHC-T cell receptor interaction and was partly dependent on T cell derived TGF-β and IL-2. Autocrine IFN-γ was required for the promotion of diabetogenic Th1 cells at high antigen doses. CONCLUSIONS/
interpretationWeak stimulation of CD4(+) T cells with DC and low-dose antigen expands a combination of antigen-specific Tregs Th2 and Tr1 cells that prevent autoimmunity, without the need to target or purify specific Treg populations.
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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.