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Physiological β Cell Death Triggers Priming of Self-reactive T Cells by Dendritic Cells in a Type-1 Diabetes Model
Open accessAbstract
The prelude to type-1 diabetes is leukocyte infiltration into the pancreatic islets, or insulitis. This process begins in pancreatic lymph nodes when T lymphocytes reactive to islet β cells encounter antigen-presenting cells (APCs) displaying peptides derived from β cell proteins. We show here that a ripple of physiological β cell death, which occurs at 2 wk of age in all mouse strains, precipitates the arrival of such APCs, and that the relevant APC is a dendritic cell of CD11c+CD11b+CD8α− phenotype. These findings have significant implications concerning the nature of the diabetes-provoking deficits in NOD mice, the identity of the primordial diabetogenic antigens, and our understanding of the balance between immunity and tolerance in a pathological context.
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Cites
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837
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How dying cells alert the immune system to danger
Kono, H., & Rock, K. L. (2008) · Nature Reviews Immunology · doi:10.1038/nri2215 · Cited by 1,737
Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death
Casares, N., Pequignot, M. O., Tesniere, A., Ghiringhelli, F., Roux, S., Chaput, N., Schmitt, E., Hamai, A., Hervas-Stubbs, S., Obeid, M., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050915 · Cited by 1,512
Genetics, pathogenesis and clinical interventions in type 1 diabetes
Bluestone, J. A., Herold, K., & Eisenbarth, G. (2010) · Nature · doi:10.1038/nature08933 · Cited by 1,265
THE NOD MOUSE: A Model of Immune Dysregulation
Anderson, M. S., & Bluestone, J. A. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115643 · Cited by 1,113
Central Role of Defective Interleukin-2 Production in the Triggering of Islet Autoimmune Destruction
Tang, Q., Adams, J. Y., Penaranda, C., Melli, K., Piaggio, E., Sgouroudis, E., Piccirillo, C. A., Salomon, B. L., & Bluestone, J. A. (2008) · Immunity · doi:10.1016/j.immuni.2008.03.016 · Cited by 729
Metadata
- Authors
- Turley, S., Poirot, L., Hattori, M., Benoist, C., & Mathis, D.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2003-11-17
- Volume
- 198
- Issue
- 10
- Pages
- 1527-1537
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2127788605
- Cited by
- 347
- References
- 1
- FWCI
- 10.72
- Type
- journal article
- Language
- en
- Open access
- green
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- Turley, S., Poirot, L., Hattori, M., Benoist, C., & Mathis, D. (2003). Physiological β Cell Death Triggers Priming of Self-reactive T Cells by Dendritic Cells in a Type-1 Diabetes Model. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20030966
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