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Beta cell-specific CD8+ T cells maintain stem cell memory-associated epigenetic programs during type 1 diabetes
Open accessAbstract
The pool of beta cell-specific CD8+ T cells in type 1 diabetes (T1D) sustains an autoreactive potential despite having access to a constant source of antigen. To investigate the long-lived nature of these cells, we established a DNA methylation-based T cell 'multipotency index' and found that beta cell-specific CD8+ T cells retained a stem-like epigenetic multipotency score. Single-cell assay for transposase-accessible chromatin using sequencing confirmed the coexistence of naive and effector-associated epigenetic programs in individual beta cell-specific CD8+ T cells. Assessment of beta cell-specific CD8+ T cell anatomical distribution and the establishment of stem-associated epigenetic programs revealed that self-reactive CD8+ T cells isolated from murine lymphoid tissue retained developmentally plastic phenotypic and epigenetic profiles relative to the same cells isolated from the pancreas. Collectively, these data provide new insight into the longevity of beta cell-specific CD8+ T cell responses and document the use of this methylation-based multipotency index for investigating human and mouse CD8+ T cell differentiation.
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“In support of our findings, a recent study found that circulating β-cell–specific CD8 T cells in T1D patients are epigenetically distinct from TCM, effector memory T (TEM) cells and exhausted CD8 T cells in chronic infection26 (for example, in HIV).”
From An autoimmune stem-like CD8 T cell population drives type 1 diabetes (2022) · cites this paper as [26]
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Metadata
- Authors
- Abdelsamed, H. A., Zebley, C. C., Nguyen, H., Rutishauser, R. L., Fan, Y., Ghoneim, H. E., Crawford, J. C., Alfei, F., Alli, S., Ribeiro, S. P., Castellaw, A. H., McGargill, M. A., Jin, H., Boi, S. K., Speake, C., Serti, E., Turka, L. A., Busch, M. E., Stone, M., Deeks, S. G., Sekaly, R.-P., Zehn, D., James, E. A., Nepom, G. T., & Youngblood, B.
- Affiliations
- St. Jude Children's Research Hospital (US)
- Benaroya Research Institute (US)
- University of California, San Francisco (US)
- Technical University of Munich (DE)
- Case Western Reserve University (US)
- Immune Tolerance Network (US)
- Harvard University (US)
- Vitalant Research Institute (US)
- Corresponding author
- Youngblood, Ben
- ORCID
- Abdelsamed, Hossam A.
- Zebley, Caitlin C.
- Nguyen, Hai
- Rutishauser, Rachel L.
- Fan, Yiping
- Ghoneim, Hazem E.
- Crawford, Jeremy Chase
- Alli, Shanta
- Ribeiro, Susan Pereira
- Castellaw, Ashley H.
- McGargill, Maureen A.
- Jin, Hongjian
- Boi, Shannon K.
- Speake, Cate
- Serti, Elisavet
- Turka, Laurence A.
- Stone, Mars
- Deeks, Steven G.
- Zehn, Dietmar
- James, Eddie A.
- Nepom, Gerald T.
- Youngblood, Ben
- Venue
- Nature Immunology
- Published
- 2020-03-30
- Volume
- 21
- Issue
- 5
- Pages
- 578-587
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC7183435
- OpenAlex
- W3013298623
- Cited by
- 121
- References
- 46
- Citations by year
- 2026: 14 · 2025: 23 · 2024: 20 · 2023: 14 · 2022: 20 · 2021: 23 · 2020: 6
- FWCI
- 9.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Department of Health & Human Services | National Institutes of Health (1R01AI114442, UM1AI109565)
- American Lebanese Syrian Associated Charities
- Assisi Foundation of Memphis
- U.S. Department of Health & Human Services | NIH | Division of Loan Repayment
- 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
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- type 1 diabetes, autoreactive T cells, DNA methylation, T cell differentiation, chromatin accessibility, T cell plasticity, T cell longevity, pancreatic beta cells
- MeSH terms
- Cell Plasticity, Adolescent, Adult, Animals, Autoantigens, Cells, Cultured, Diabetes Mellitus, Type 1, Female, Flow Cytometry, Humans, Immunologic Memory, Male, CD8-Positive T-Lymphocytes, DNA Methylation, Pluripotent Stem Cells, Epigenesis, Genetic, Insulin-Secreting Cells, Mice, Young Adult, Single-Cell Analysis
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