Beta cell-specific CD8+ T cells maintain stem-cell memory-associated epigenetic programs during type 1 diabetes
| العنوان: | Beta cell-specific CD8+ T cells maintain stem-cell memory-associated epigenetic programs during type 1 diabetes |
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| المؤلفون: | Rafick-Pierre Sekaly, Elisavet Serti, Shannon K. Boi, Ashley H. Castellaw, Dietmar Zehn, Hai Nguyen, Hazem E. Ghoneim, Caitlin C. Zebley, Michael E. Busch, Mars Stone, Rachel L. Rutishauser, Francesca Alfei, Eddie A. James, Maureen A. McGargill, Cate Speake, Ben Youngblood, Jeremy Chase Crawford, Yiping Fan, Gerald T. Nepom, Steven G. Deeks, Hossam A. Abdelsamed, Susan Pereira Ribeiro, Shanta Alli, Hongjian Jin, Laurence A. Turka |
| المصدر: | Nature immunology Nature immunology, vol 21, iss 5 Nature Immunology |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Cell Plasticity, CD8-Positive T-Lymphocytes, Regenerative Medicine, Autoantigens, Epigenesis, Genetic, Mice, 0302 clinical medicine, Stem Cell Research - Nonembryonic - Human, Insulin-Secreting Cells, 2.1 Biological and endogenous factors, Immunology and Allergy, Cytotoxic T cell, Aetiology, Cells, Cultured, Cultured, Diabetes, Acquired immune system, Flow Cytometry, Cell biology, medicine.anatomical_structure, Female, Stem cell, Beta cell, Single-Cell Analysis, Type 1, Adult, Pluripotent Stem Cells, Adolescent, Cells, T cell, Immunology, Biology, Autoimmune Disease, Article, 03 medical and health sciences, Young Adult, Genetic, Diabetes Mellitus, Genetics, medicine, Animals, Humans, Epigenetics, Metabolic and endocrine, DNA Methylation, Stem Cell Research, 030104 developmental biology, Diabetes Mellitus, Type 1, T cell differentiation, Immunologic Memory, CD8, Epigenesis, 030215 immunology |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1529-2916 1529-2908 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::89c766e2ff25c8b1dacf4caad1134276Test http://europepmc.org/articles/PMC7183435Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....89c766e2ff25c8b1dacf4caad1134276 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15292916 15292908 |
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