The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
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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Cites
Epigenetic modifications and human disease
Portela, A., & Esteller, M. (2010) · Nature Biotechnology · doi:10.1038/nbt.1685 · Cited by 2,938
The molecular hallmarks of epigenetic control
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Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation
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A human memory T cell subset with stem cell–like properties
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Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus
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BSMAP: whole genome bisulfite sequence MAPping program
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An anti-CD3 antibody, teplizumab, in relatives at risk for type 1 diabetes
Herold, K. C., Bundy, B. N., Long, S. A., Bluestone, J. A., DiMeglio, L. A., Dufort, M. J., Gitelman, S. E., Gottlieb, P. A., Krischer, J. P., Linsley, P. S., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1902226 · Cited by 1,189
TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection
Alfei, F., Kanev, K., Hofmann, M., Wu, M., Ghoneim, H. E., Roelli, P., Utzschneider, D. T., von Hoesslin, M., Cullen, J. G., Fan, Y., et al. (2019) · Nature · doi:10.1038/s41586-019-1326-9 · Cited by 930
Self-citationDe Novo Epigenetic Programs Inhibit PD-1 Blockade-Mediated T Cell Rejuvenation
Ghoneim, H. E., Fan, Y., Moustaki, A., Abdelsamed, H. A., Dash, P., Dogra, P., Carter, R., Awad, W., Neale, G. A. M., Thomas, P. G., et al. (2017) · Cell · doi:10.1016/j.cell.2017.06.007 · Cited by 808
Self-citationAnalysis of islet inflammation in human type 1 diabetes
Willcox, A., Richardson, S. J., Bone, A. J., Foulis, A. K., & Morgan, N. G. (2009) · Clinical and Experimental Immunology · doi:10.1111/j.1365-2249.2008.03860.x · Cited by 712
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An anti-CD3 antibody, teplizumab, in relatives at risk for type 1 diabetes
Herold, K. C., Bundy, B. N., Long, S. A., Bluestone, J. A., DiMeglio, L. A., Dufort, M. J., Gitelman, S. E., Gottlieb, P. A., Krischer, J. P., Linsley, P. S., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1902226 · Cited by 1,189
Deleting DNMT3A in CAR T cells prevents exhaustion and enhances antitumor activity
Prinzing, B., Zebley, C. C., Petersen, C. T., Fan, Y., Anido, A. A., Yi, Z., Nguyen, P., Houke, H., Bell, M., Haydar, D., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abh0272 · Cited by 349
Self-citationAn autoimmune stem-like CD8 T cell population drives type 1 diabetes
Gearty, S. V., Dündar, F., Zumbo, P., Espinosa-Carrasco, G., Shakiba, M., Sanchez-Rivera, F. J., Socci, N. D., Trivedi, P., Lowe, S. W., Lauer, P., et al. (2022) · Nature · doi:10.1038/s41586-021-04248-x · Cited by 257
Collier, J. L., Weiss, S. A., Pauken, K. E., Sen, D. R., & Sharpe, A. H. (2021) · Nature Immunology · doi:10.1038/s41590-021-00949-7 · Cited by 237
The immunology of type 1 diabetes
Herold, K. C., Delong, T., Perdigoto, A. L., Biru, N., Brusko, T. M., & Walker, L. S. K. (2024) · Nature reviews. Immunology · doi:10.1038/s41577-023-00985-4 · Cited by 241
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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