The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Proinsulin-Specific, HLA-DQ8, and HLA-DQ8-Transdimer–Restricted CD4+ T Cells Infiltrate Islets in Type 1 Diabetes
Abstract
Type 1 diabetes (T1D) develops when insulin-secreting β-cells, found in the pancreatic islets of Langerhans, are destroyed by infiltrating T cells. How human T cells recognize β-cell-derived antigens remains unclear. Genetic studies have shown that HLA and insulin alleles are the most strongly associated with risk of T1D. These long-standing observations implicate CD4+ T-cell responses against (pro)insulin in the pathogenesis of T1D. To dissect the autoimmune T-cell response against human β-cells, we isolated and characterized 53 CD4+ T-cell clones from within the residual pancreatic islets of a deceased organ donor who had T1D. These 53 clones expressed 47 unique clonotypes, 8 of which encoded proinsulin-specific T-cell receptors. On an individual clone basis, 14 of 53 CD4+ T-cell clones (26%) recognized 6 distinct but overlapping epitopes in the C-peptide of proinsulin. These clones recognized C-peptide epitopes presented by HLA-DQ8 and, notably, HLA-DQ8 transdimers that form in HLA-DQ2/-DQ8 heterozygous individuals. Responses to these epitopes were detected in the peripheral blood mononuclear cells of some people with recent-onset T1D but not in HLA-matched control subjects. Hence, proinsulin-specific, HLA-DQ8, and HLA-DQ8-transdimer–restricted CD4+ T cells are strongly implicated in the autoimmune pathogenesis of human T1D.
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Insulin antibodies in insulin-dependent diabetics before insulin treatment
Palmer, J. P., Asplin, C. M., Clemons, P., Lyen, K., Tatpati, O., Raghu, P. K., & Paquette, T. L. (1983) · Science · doi:10.1126/science.6362005 · Cited by 1,078
Pugliese, A., Zeller, M., Fernandez, A., Zalcberg, L. J., Bartlett, R. J., Ricordi, C., Pietropaolo, M., Eisenbarth, G. S., Bennett, S. T., & Patel, D. D. (1997) · Nature Genetics · doi:10.1038/ng0397-293 · Cited by 945
Bennett, S. T., Lucassen, A. M., Gough, S. C. L., Powell, E. E., Undlien, D. E., Pritchard, L. E., Merriman, M. E., Kawaguchi, Y., Dronsfield, M. J., Pociot, F., et al. (1995) · Nature Genetics · doi:10.1038/ng0395-284 · Cited by 746
Kent, S. C., Chen, Y., Bregoli, L., Clemmings, S. M., Kenyon, N. S., Ricordi, C., Hering, B. J., & Hafler, D. A. (2005) · Nature · doi:10.1038/nature03625 · Cited by 409
Noble, J. A., & Erlich, H. A. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a007732 · Cited by 335
Wang, G. C., Dash, P., McCullers, J. A., Doherty, P. C., & Thomas, P. G. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003647 · Cited by 238
Cited by
Pathogenic CD4 T cells in type 1 diabetes recognize epitopes formed by peptide fusion
Delong, T., Wiles, T. A., Baker, R. L., Bradley, B., Barbour, G., Reisdorph, R., Armstrong, M., Powell, R. L., Reisdorph, N., Kumar, N., et al. (2016) · Science · doi:10.1126/science.aad2791 · Cited by 503
Self-citationThe heterogeneous pathogenesis of type 1 diabetes mellitus
Ilonen, J., Lempainen, J., & Veijola, R. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0254-y · Cited by 494
Babon, J. A. B., DeNicola, M. E., Blodgett, D. M., Crèvecoeur, I., Buttrick, T. S., Maehr, R., Bottino, R., Naji, A., Kaddis, J., Elyaman, W., et al. (2016) · Nature Medicine · doi:10.1038/nm.4203 · Cited by 300
New frontiers in the treatment of type 1 diabetes
Warshauer, J. T., Bluestone, J. A., & Anderson, M. S. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2019.11.017 · Cited by 259
Wen, X., Yang, J., James, E., Chow, I.-T., Reijonen, H., & Kwok, W. W. (2020) · Science Immunology · doi:10.1126/sciimmunol.aax8767 · Cited by 35
Metadata
- Authors
- Pathiraja, V., Kuehlich, J. P., Campbell, P. D., Krishnamurthy, B., Loudovaris, T., Coates, P. T. H., Brodnicki, T. C., O’Connell, P. J., Kedzierska, K., Rodda, C., Bergman, P., Hill, E., Purcell, A. W., Dudek, N. L., Thomas, H. E., Kay, T. W. H., & Mannering, S. I.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2014-08-25
- Volume
- 64
- Issue
- 1
- Pages
- 172-182
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2097853505
- Cited by
- 165
- References
- 6
- FWCI
- 8.52
- Type
- journal article
- Language
- en
- Open access
- closed
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- Pathiraja, V., Kuehlich, J. P., Campbell, P. D., Krishnamurthy, B., Loudovaris, T., Coates, P. T. H., Brodnicki, T. C., O’Connell, P. J., Kedzierska, K., Rodda, C., Bergman, P., Hill, E., Purcell, A. W., Dudek, N. L., Thomas, H. E., Kay, T. W. H., & Mannering, S. I. (2015). Proinsulin-Specific, HLA-DQ8, and HLA-DQ8-Transdimer–Restricted CD4+ T Cells Infiltrate Islets in Type 1 Diabetes. Diabetes. https://doi.org/10.2337/db14-0858
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