Autoreactive T effector memory differentiation mirrors β cell function in type 1 diabetes
| Autor: | Craig A. Beam, Lorraine Yeo, Mark Peakman, Martin Eichmann, Alyssa Woodwyk, Garry Dolton, Alka Saxena, Rossella Melchiotti, Sanjana Sood, Irma Pujol-Autonell, Andrew K. Sewell, Ania Skowera, Efthymios Fidanis, Katie Tungatt, Anna Lorenc, Susanne Heck |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male T cell Islets of Langerhans Transplantation CD8-Positive T-Lymphocytes medicine.disease_cause Autoimmunity Islets of Langerhans 03 medical and health sciences 0302 clinical medicine Memory Insulin-Secreting Cells medicine Cytotoxic T cell Humans Child Effector Chemistry Pancreatic islets CD28 Cell Differentiation General Medicine Cell biology Granzyme B 030104 developmental biology medicine.anatomical_structure Diabetes Mellitus Type 1 Female Immunologic Memory CD8 Research Article 030215 immunology |
| Zdroj: | Journal of Clinical Investigation Yeo, L, Woodwyk, A, Sood, S, Lorenc, A, Eichmann, M, Pujol-Autonell, I, Melchiotti, R, Skowera, A, Fidanis, E, Dolton, G M, Tungatt, K, Sewell, A K, Heck, S, Saxena, A, Beam, C A & Peakman, M 2018, ' Autoreactive T effector memory differentiation mirrors β cell function in type 1 diabetes ', Journal of Clinical Investigation, vol. 128, no. 8, pp. 3460-3474 . https://doi.org/10.1172/JCI120555 |
| ISSN: | 1558-8238 0021-9738 |
| Popis: | In type 1 diabetes, cytotoxic CD8+ T cells with specificity for β cell autoantigens are found in the pancreatic islets, where they are implicated in the destruction of insulin-secreting β cells. In contrast, the disease relevance of β cell-reactive CD8+ T cells that are detectable in the circulation, and their relationship to β cell function, are not known. Here, we tracked multiple, circulating β cell-reactive CD8+ T cell subsets and measured β cell function longitudinally for 2 years, starting immediately after diagnosis of type 1 diabetes. We found that change in β cell-specific effector memory CD8+ T cells expressing CD57 was positively correlated with C-peptide change in subjects below 12 years of age. Autoreactive CD57+ effector memory CD8+ T cells bore the signature of enhanced effector function (higher expression of granzyme B, killer-specific protein of 37 kDa, and CD16, and reduced expression of CD28) compared with their CD57-counterparts, and network association modeling indicated that the dynamics of β cell-reactive CD57+ effector memory CD8+ T cell subsets were strongly linked. Thus, coordinated changes in circulating β cell-specific CD8+ T cells within the CD57+ effector memory subset calibrate to functional insulin reserve in type 1 diabetes, providing a tool for immune monitoring and a mechanism-based target for immunotherapy. |
| Databáze: | OpenAIRE |
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