Type 1 Diabetes in BioBreeding Rats Is Critically Linked to an Imbalance between Th17 and Regulatory T Cells and an Altered TCR Repertoire
Open accessAbstract
Diabetes-prone BioBreeding (DP-BB) rats spontaneously develop type 1 diabetes mellitus (T1DM) on grounds of their MHC haplotype RT1u and a point mutation in the Gimap5 gene. In this study, we report that DP-BB rats exhibit an increasingly severe imbalance, in particular between Th17 and regulatory T (Treg) cells, within the first months of age. This can be assigned to an excess in effector T cells because neither the percentage nor the function of the Treg cells is compromised. Flow cytometric analysis of Vβ segment usage and CDR3 spectratyping further suggest that the disturbed repertoire of peripheral T cells may also contribute to the development of T1DM in DP-BB rats. Importantly, expansion of Treg cells in vivo by means of a CD28 superagonistic Ab as well as adoptive transfer of Treg cells efficiently interferes with the development of T1DM in DP-BB rats, whereas treatment with conventional Th cells does not afford protection. Using a newly generated strain of enhanced GFP transgenic rats, we could further demonstrate that the transferred Treg cells persist in the recipient rats for several months and partially correct the imbalance between Th17 and Treg cells. Thus, our data support the hypothesis that unchecked effector T cell action and a disturbed T cell repertoire contribute to the development of T1DM in DP-BB rats, which may also have implications for a better understanding of the human disease.
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CD28 superagonist therapy has been efficacious in a large number of rat and mouse disease models, as reported in 25 original publications.
“leading, as of today, to 25 original publications describing efficacious therapy in a large number of rat and mouse disease models”
From The rise and fall of the <scp>CD</scp> 28 superagonist <scp>TGN</scp> 1412 and its return as <scp>TAB</scp> 08: a personal account (2016) · cites this paper as [6]
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References 55 · Cited by 54
- Authors
- van den Brandt, J., Fischer, H. J., Walter, L., Hünig, T., Klöting, I., & Reichardt, H. M.
- Affiliations
- Department of Cellular and Molecular Immunology, University of Göttingen Medical School , Göttingen
- Universitätsmedizin Göttingen (DE)
- German Primate Center (DE)
- University of Würzburg (DE)
- Universität Greifswald (DE)
- Corresponding author
- Reichardt, Holger M
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-08
- Volume
- 185
- Issue
- 4
- Pages
- 2285-2294
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2104298924
- Cited by
- 54
- References
- 55
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 1 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 3 · 2016: 5 · 2015: 7 · 2014: 7 · 2013: 4 · 2012: 8
- FWCI
- 3.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- GRO (submittedVersion)
- 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
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- type 1 diabetes, BioBreeding rat, Th17 cells, regulatory T cells, T cell receptor repertoire, GIMAP5, adoptive transfer, effector T cells, CDR3 spectratyping, autoimmunity
- MeSH terms
- Animals, Cell Line, Diabetes Mellitus, Type 1, Female, Flow Cytometry, T-Lymphocytes, Helper-Inducer, Humans, Lymphopenia, Male, Mutation, Rats, Inbred BB, Receptors, Antigen, T-Cell, T-Lymphocytes, Lymphocyte Count, GTP-Binding Proteins, Adoptive Transfer, Interleukin-17, Green Fluorescent Proteins, T-Lymphocytes, Regulatory, Rats, Interleukin-2 Receptor alpha Subunit, Rats, Transgenic
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