Expansion of functional endogenous antigen-specific CD4+CD25+ regulatory T cells from nonobese diabetic mice
Open accessAbstract
CD4+CD25+Foxp3+ regulatory T cells (Treg) are critical for controlling autoimmunity. Evidence suggests that Treg development, peripheral maintenance, and suppressive function are dependent on Ag specificity. However, there is little direct evidence that the Treg responsible for controlling autoimmunity in NOD mice or other natural settings are Ag specific. In fact, some investigators have argued that polyclonal Ag-nonspecific Treg are efficient regulators of immunity. Thus, the goal of this study was to identify, expand, and characterize islet Ag-specific Treg in NOD mice. Ag-specific Treg from NOD mice were efficiently expanded in vitro using IL-2 and beads coated with recombinant islet peptide mimic-MHC class II and anti-CD28 mAb. The expanded Ag-specific Treg expressed prototypic surface markers and cytokines. Although activated in an Ag-specific fashion, the expanded Treg were capable of bystander suppression both in vitro and in vivo. Importantly, the islet peptide mimic-specific Treg were more efficient than polyclonal Treg in suppressing autoimmune diabetes. These results provide a direct demonstration of the presence of autoantigen-specific Treg in the natural setting that can be applied as therapeutics for organ-specific autoimmunity.
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Regulatory CD4+CD25+ T cells play an important role in prevention of autoimmune diseases.
“Regulatory CD4+CD25+ T cells play an important role in prevention of autoimmune diseases.[1]”
From TGN1412: From Discovery to Disaster (2010) · cites this paper as [1]
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“Regulatory CD4+CD25+ T cells play an important role in prevention of autoimmune diseases.[1] Activation of regulatory T cells by antigens is controlled by co-stimulatory signal from antigen presenting cells, mainly dendritic cells (DC) where antigen is presented by MHC complex of DC to T cells via T-cell receptor.”
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- Authors
- Masteller, E. L., Warner, M. R., Tang, Q., Tarbell, K. V., McDevitt, H., & Bluestone, J. A.
- Affiliations
- University of California, San Francisco (US)
- Stanford Medicine (US)
- Corresponding author
- Tang, Qizhi
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-09-01
- Volume
- 175
- Issue
- 5
- Pages
- 3053-3059
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1629285726
- Cited by
- 260
- References
- 17
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 8 · 2023: 12 · 2022: 9 · 2021: 9 · 2020: 9 · 2019: 6 · 2018: 6 · 2017: 10 · 2016: 7 · 2015: 8 · 2014: 10 · 2013: 8 · 2012: 12
- FWCI
- 10.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (U19AI056388, U19 AI56388)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30-DK-63720, P30DK063720)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- regulatory T cells, CD4+CD25+Foxp3+ T cells, islet antigens, NOD mice, autoimmune diabetes, bystander suppression, autoimmunity, Treg therapy
- MeSH terms
- Animals, Autoantigens, Diabetes Mellitus, Type 1, Immune Tolerance, Receptors, Interleukin-2, Cytokines, Mice, Inbred NOD, Receptors, Antigen, T-Cell, alpha-beta, CD28 Antigens, T-Lymphocytes, Regulatory, Mice
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