Demonstration of Tissue Resident Memory CD8 T Cells in Insulitic Lesions in Adult Patients with Recent-Onset Type 1 Diabetes
Open accessAbstract
Subtypes of CD8+ T cells in insulitic lesions in biopsy specimens from six subjects with recent-onset type 1 diabetes (T1D) and six nondiabetic matched controls were analyzed using simultaneous multicolor immunofluorescence. Also, insulitic islets based on accumulation of CD3+ T cells were microdissected with laser-capture microscopy, and gene transcripts associated with inflammation and autoimmunity were analyzed. We found a substantial proportion, 43%, of the CD8+ T cells in the insulitic lesions to display a tissue resident memory T cell (T RM) (CD8+CD69+CD103+) phenotype in T1D subjects. Most T RM cells were located in the insulitic lesion in the endocrine-exocrine interface. T RM cells were also sporadically found in islets of control subjects. Moreover, gene expression analysis showed a lack of active transcription of genes associated with acute inflammatory or cytotoxic T-cell responses. We present evidence that a substantial proportion of T cells in insulitic lesions of recent-onset T1D patients are T RM cells and not classic cytotoxic CD8+ T cells. Our findings highlight the need for further analysis of the T cells involved in insulitis to elucidate their role in the etiology of T1D.
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In organs other than the heart, TRM cells have been incriminated as key drivers of autoimmune diseases including psoriasis, vitiligo, type 1 diabetes, idiopathic arthritis, Alzheimer disease, and multiple sclerosis.
“Moreover, in other organs than the heart, T RM cells have been incriminated as key drivers of autoimmune diseases including psoriasis, vitiligo, type 1 diabetes, idiopathic arthritis, Alzheimer disease, and multiple sclerosis. 294,302-310”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [305]
The Discussion (article pp. 581–588) reports TRM cells in insulitic lesions of adults with recent-onset type 1 diabetes and suggests they may have a significant role, but does not establish them as key drivers. It also mentions psoriasis and vitiligo lesions, but the supplied passages do not support the claim for idiopathic arthritis, Alzheimer disease, or multiple sclerosis. (LLM, conf=0.88)
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Autoreactive CD8+ T cells are restrained by an exhaustion-like program that is maintained by LAG3
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- Authors
- Kuric, E., Seiron, P., Krogvold, L., Edwin, B., Buanes, T., Hanssen, K. F., Skog, O., Dahl-Jørgensen, K., & Korsgren, O.
- Affiliations
- Uppsala University (SE)
- Oslo University Hospital (NO)
- Corresponding author
- Kuric, Enida
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 187
- Issue
- 3
- Pages
- 581-588
- ISSN
- 0002-9440 (ISSN-L)
- OpenAlex
- W2588544503
- Cited by
- 80
- References
- 5
- Citations by year
- 2026: 4 · 2025: 14 · 2024: 8 · 2023: 9 · 2022: 8 · 2021: 12 · 2020: 5 · 2019: 5 · 2018: 9 · 2017: 6
- FWCI
- 4.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Åke Wiberg Stiftelse
- Gillbergska stiftelsen
- Tore Nilsons Stiftelse för Medicinsk Forskning
- European Commission (2007–2013, FP7 2007-2013, 261441, FP7/2007)
- Novo Nordisk
- Barndiabetesfonden
- Uppsala Universitet
- Novo Nordisk Fonden (NNF17OC0027314, NNF14OC0010935, NNF16OC0021334)
- Medical Research Council
- Helse Sør-Øst RHF
- 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 › Surgery › Pancreatic function and diabetes
- Keywords
- type 1 diabetes, insulitis, tissue-resident memory T cells, CD8+ T cells, CD69, CD103, pancreatic islets, autoimmunity, inflammation, cytotoxic T lymphocytes, gene expression
- MeSH terms
- Adult, Diabetes Mellitus, Type 1, Female, Gene Expression Regulation, Humans, Immunologic Memory, Inflammation, Insulin, Male, Autoimmunity, CD8-Positive T-Lymphocytes
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