Central Role of Defective Interleukin-2 Production in the Triggering of Islet Autoimmune Destruction
Open accessAbstract
The dynamics of CD4(+) effector T cells (Teff cells) and CD4(+)Foxp3(+) regulatory T cells (Treg cells) during diabetes progression in nonobese diabetic mice was investigated to determine whether an imbalance of Treg cells and Teff cells contributes to the development of type 1 diabetes. Our results demonstrated a progressive decrease in the Treg cell:Teff cell ratio in inflamed islets but not in pancreatic lymph nodes. Intra-islet Treg cells expressed reduced amounts of CD25 and Bcl-2, suggesting that their decline was due to increased apoptosis. Additionally, administration of low-dose interleukin-2 (IL-2) promoted Treg cell survival and protected mice from developing diabetes. Together, these results suggest intra-islet Treg cell dysfunction secondary to defective IL-2 production is a root cause of the progressive breakdown of self-tolerance and the development of diabetes in nonobese diabetic mice.
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Peculiarities of the autoimmune attack during EAE and/or primary proneness to axonopathy in NOD mice are implicated in the cause of disease progression.
“Rather, the present study, along with data showing an impairment of the T regulatory response in NOD mice (Tang et al. 2008), point to peculiarities of the autoimmune attack during EAE and/or primary proneness to axonopathy in this mouse strain.”
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- Authors
- Tang, Q., Adams, J. Y., Penaranda, C., Melli, K., Piaggio, E., Sgouroudis, E., Piccirillo, C. A., Salomon, B. L., & Bluestone, J. A.
- Affiliations
- University of California, San Francisco (US)
- Centre National de la Recherche Scientifique (FR)
- McGill University (CA)
- Corresponding author
- Bluestone, Jeffrey A.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2008-05
- Volume
- 28
- Issue
- 5
- Pages
- 687-697
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC2394854
- OpenAlex
- W2162675860
- Cited by
- 729
- References
- 0
- Citations by year
- 2026: 13 · 2025: 17 · 2024: 21 · 2023: 19 · 2022: 25 · 2021: 41 · 2020: 35 · 2019: 36 · 2018: 39 · 2017: 31 · 2016: 48 · 2015: 54 · 2014: 54 · 2013: 59 · 2012: 48
- FWCI
- 35.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1903 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Canadian Diabetes Association
- Canadian Institutes of Health Research
- National Institutes of Health
- Howard Hughes Medical Institute
- Juvenile Diabetes Research Foundation Australia
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- type 1 diabetes, interleukin-2, regulatory T cells, effector T cells, CD25, Bcl-2, islet autoimmunity, self-tolerance breakdown, NOD mice
- MeSH terms
- Animals, Cell Survival, Diabetes Mellitus, Type 1, Interleukin-2, Islets of Langerhans, Lymph Nodes, Lymphocyte Activation, CD4-Positive T-Lymphocytes, Autoimmunity, Mice, Inbred NOD, Proto-Oncogene Proteins c-bcl-2, T-Lymphocytes, Regulatory, Mice, Interleukin-2 Receptor alpha Subunit
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