Abstract | OBJECTIVE: METHODS: To increase the antigen presentation of GPI, we generated transgenic mice expressing a membrane-bound form of GPI (mGPI) and crossed them with K/BxN mice. A monoclonal antibody specific for the α-chain of the KRN T cell receptor was generated to examine the fate of GPI-specific T cells. RESULTS: The mGPI-transgenic mice presented GPI more efficiently and showed a dramatic increase in negative selection and an inhibition of arthritis. Interestingly, thymic negative selection remained incomplete in these mice, and the escaped autoreactive T cells were anergic in the peripheral lymphoid organs, suggesting that enhanced antigen presentation also induces peripheral tolerance. Despite this apparent tolerance induction toward GPI, these mice developed a chronic wasting disease, characterized by colonic inflammation with epithelial dysplasia, as well as a dramatic reduction in Treg cells. CONCLUSION: These data indicate that insufficient autoantigen expression or presentation results in defects of both central and peripheral tolerance in the K/BxN mice. Our findings also support the idea that insufficient autoantigen levels may underlie the development of autoimmunity.
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Authors | Jason Perera, Xiao Liu, Yuzhen Zhou, Nora E Joseph, Liping Meng, Jerrold R Turner, Haochu Huang |
Journal | Arthritis and rheumatism
(Arthritis Rheum)
Vol. 65
Issue 11
Pg. 2847-56
(Nov 2013)
ISSN: 1529-0131 [Electronic] United States |
PMID | 23840022
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Copyright © 2013 by the American College of Rheumatology. |
Chemical References |
- Antibodies, Monoclonal
- Autoantigens
- Cytokines
- Glucose-6-Phosphate Isomerase
- Gpi1 protein, mouse
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Topics |
- Animals
- Antibodies, Monoclonal
(immunology)
- Antigen Presentation
(immunology)
- Arthritis, Rheumatoid
(immunology)
- Autoantigens
(immunology)
- Bone Marrow Cells
(cytology, immunology)
- Cytokines
(genetics, immunology)
- Disease Models, Animal
- Glucose-6-Phosphate Isomerase
(genetics, immunology)
- Immune Tolerance
(immunology)
- Mice
- Mice, Transgenic
- T-Lymphocytes, Regulatory
(cytology, immunology)
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