Ectopic Expression of Self-Antigen Drives Regulatory T Cell Development and Not Deletion of Autoimmune T Cells
| العنوان: | Ectopic Expression of Self-Antigen Drives Regulatory T Cell Development and Not Deletion of Autoimmune T Cells |
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| المؤلفون: | Maran L. Sprouse, Pinaki P. Banerjee, Thomas Lee, Matthew L. Bettini, Maria Bettini |
| المصدر: | The Journal of Immunology. 199:2270-2278 |
| بيانات النشر: | The American Association of Immunologists, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | CD4-Positive T-Lymphocytes, 0301 basic medicine, Regulatory T cell, T cell, Immunology, Autoimmunity, Biology, Autoantigens, T-Lymphocytes, Regulatory, Article, Autoimmune Diseases, Ectopic Gene Expression, Mice, 03 medical and health sciences, Interleukin 21, 0302 clinical medicine, Insulin-Secreting Cells, medicine, Animals, Insulin, Immunology and Allergy, Cytotoxic T cell, IL-2 receptor, Antigen-presenting cell, Thymocytes, FOXP3, Cell Differentiation, Natural killer T cell, Peptide Fragments, Cell biology, Diabetes Mellitus, Type 1, 030104 developmental biology, medicine.anatomical_structure, 030215 immunology |
| الوصف: | Type 1 diabetes is a T cell–mediated autoimmune disease that is characterized by Ag-specific targeting and destruction of insulin-producing β cells. Although multiple studies have characterized the pathogenic potential of β cell–specific T cells, we have limited mechanistic insight into self-reactive autoimmune T cell development and their escape from negative selection in the thymus. In this study, we demonstrate that ectopic expression of insulin epitope B:9–23 (InsB9–23) by thymic APCs is insufficient to induce deletion of high- or low-affinity InsB9–23–reactive CD4+ T cells; however, we observe an increase in the proportion and number of thymic and peripheral Foxp3+ regulatory T cells. In contrast, the MHC stable insulin mimetope (InsB9–23 R22E) efficiently deletes insulin-specific T cells and prevents escape of high-affinity thymocytes. Collectively, these results suggest that Ag dose and peptide–MHC complex stability can lead to multiple fates of insulin-reactive CD4+ T cell development and autoimmune disease outcome. |
| تدمد: | 1550-6606 0022-1767 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2e60351aa1f3f957fb8b7532c12d5609Test https://doi.org/10.4049/jimmunol.1700207Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2e60351aa1f3f957fb8b7532c12d5609 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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