Expanded T cells from pancreatic lymph nodes of type 1 diabetic subjects recognize an insulin epitope
Abstract
In autoimmune type 1 diabetes, pathogenic T lymphocytes are associated with the specific destruction of insulin-producing beta-islet cells. Identification of the autoantigens involved in triggering this process is a central question. Here we examined T cells from pancreatic draining lymph nodes, the site of islet-cell-specific self-antigen presentation. We cloned single T cells in a non-biased manner from pancreatic draining lymph nodes of subjects with type 1 diabetes and from non-diabetic controls. A high degree of T-cell clonal expansion was observed in pancreatic lymph nodes from long-term diabetic patients but not from control subjects. The oligoclonally expanded T cells from diabetic subjects with DR4, a susceptibility allele for type 1 diabetes, recognized the insulin A 1-15 epitope restricted by DR4. These results identify insulin-reactive, clonally expanded T cells from the site of autoinflammatory drainage in long-term type 1 diabetics, indicating that insulin may indeed be the target antigen causing autoimmune diabetes.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
This finding, combined with independent investigations in humans and rodent models, supports the growing notion that proinsulin is a key autoantigen in type 1 diabetes.
“This finding, combined with an extensive series of independent investigations in humans and in rodent models of type 1 diabetes, support the growing notion that proinsulin is a key autoantigen in the disease;69”
From Type 1 diabetes (2014) · cites this paper as [69]
Cites
the FinnDiane Study Group, Hermann, R., Knip, M., Veijola, R., Simell, O., Laine, A.-P., Åkerblom, H. K., Groop, P.-H., Forsblom, C., Pettersson-Fernholm, K., et al. (2003) · Diabetologia · doi:10.1007/s00125-003-1045-4 · Cited by 245 · see citing works
Thrailkill, K. M., Quattrin, T., Baker, L., Kuntze, J. E., Compton, P. G., & Martha, P. M. (1999) · Diabetes Care · doi:10.2337/diacare.22.4.585 · Cited by 88 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Atkinson, M. A., Eisenbarth, G. S., & Michels, A. W. (2014) · The Lancet · doi:10.1016/s0140-6736(13)60591-7 · Cited by 2,713 · see citing works
T cell responses: naïve to memory and everything in between
Pennock, N. D., White, J. T., Cross, E. W., Cheney, E. E., Tamburini, B. A., & Kedl, R. M. (2013) · Advances in Physiology Education · doi:10.1152/advan.00066.2013 · Cited by 461 · see citing works
Mohr, S. B., Garland, C. F., Gorham, E. D., & Garland, F. C. (2008) · Diabetologia · doi:10.1007/s00125-008-1061-5 · Cited by 330 · see citing works
Understanding type 1 diabetes through genetics: advances and prospects
Polychronakos, C., & Li, Q. (2011) · Nature Reviews Genetics · doi:10.1038/nrg3069 · Cited by 226 · see citing works
Rother, K. I., Spain, L. M., Wesley, R. A., Digon, B. J., Baron, A., Chen, K., Nelson, P., Dosch, H.-M., Palmer, J. P., Brooks-Worrell, B., et al. (2009) · Diabetes Care · doi:10.2337/dc09-0773 · Cited by 133 · see citing works
Autoreactive CD8+ T cells are restrained by an exhaustion-like program that is maintained by LAG3
Grebinoski, S., Zhang, Q., Cillo, A. R., Manne, S., Xiao, H., Brunazzi, E. A., Tabib, T., Cardello, C., Lian, C. G., Murphy, G. F., et al. (2022) · Nature Immunology · doi:10.1038/s41590-022-01210-5 · Cited by 107 · see citing works
Cantú-Rodríguez, O. G., Lavalle-González, F., Herrera-Rojas, M. Á., Jaime-Pérez, J. C., Hawing-Zárate, J. Á., Gutiérrez-Aguirre, C. H., Mancias-Guerra, C., González-Llano, O., Zapata-Garrido, A., Villarreal-Pérez, J. Z., et al. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-2776 · Cited by 39 · see citing works
Immunomodulation with human recombinant autoantigens
Lernmark, Å., & Agardh, C.-D. (2005) · Trends in Immunology · doi:10.1016/j.it.2005.08.015 · Cited by 24 · see citing works
Yang, J. H. M., Ward‐Hartstonge, K. A., Perry, D. J., Blanchfield, J. L., Posgai, A. L., Wiedeman, A. E., Diggins, K., Rahman, A., Tree, T. I. M., Brusko, T. M., et al. (2022) · European Journal of Immunology · doi:10.1002/eji.202049067 · Cited by 16 · see citing works
Self-citation
- Authors
- Kent, S. C., Chen, Y., Bregoli, L., Clemmings, S. M., Kenyon, N. S., Ricordi, C., Hering, B. J., & Hafler, D. A.
- Affiliations
- Brigham and Women's Hospital (US)
- University of Minnesota (US)
- University of Miami (US)
- Corresponding author
- Hafler, David A.
- ORCID
- Venue
- Nature
- Published
- 2005-05
- Volume
- 435
- Issue
- 7039
- Pages
- 224-228
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1981165130
- Cited by
- 409
- References
- 2
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 5 · 2023: 15 · 2022: 7 · 2021: 9 · 2020: 7 · 2019: 21 · 2018: 9 · 2017: 19 · 2016: 14 · 2015: 23 · 2014: 14 · 2013: 16 · 2012: 27
- FWCI
- 26.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (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
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- type 1 diabetes, insulin autoantigen, T cell clonal expansion, HLA-DR4, autoimmunity, beta cell destruction, NOD mice, autoantibodies, islet transplantation, antigen-specific immunotherapy
- MeSH terms
- Alleles, Amino Acid Sequence, Clone Cells, Diabetes Mellitus, Type 1, HLA-DR Antigens, Humans, Insulin, Lymph Nodes, Molecular Sequence Data, Pancreas, Receptors, Antigen, T-Cell, Substrate Specificity, T-Lymphocytes, Case-Control Studies, Epitopes, T-Lymphocyte, HLA-DRB1 Chains
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
