ZnT8 Is a Major CD8+ T Cell–Recognized Autoantigen in Pediatric Type 1 Diabetes
| العنوان: | ZnT8 Is a Major CD8+ T Cell–Recognized Autoantigen in Pediatric Type 1 Diabetes |
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| المؤلفون: | Yamina Hamel, Roland Kratzer, Emmanuelle Énée, Lucienne Chatenoud, Benedicte Michaud, Peter van Endert, Émilie Barilleau, Christophe Marchi, Jean-Jacques Robert, Jean-Baptiste Arnoux, Jacques Beltrand |
| المساهمون: | U 1013, Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté de Médecine, Université de Ngozi, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), ProdInra, Migration |
| المصدر: | Diabetes Diabetes, American Diabetes Association, 2012, 61 (7), pp.1779-1784. ⟨10.2337/db12-0071⟩ |
| بيانات النشر: | American Diabetes Association, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Male, Enzyme-Linked Immunospot Assay, AUTOIMMUNITY, Endocrinology, Diabetes and Metabolism, CD8-Positive T-Lymphocytes, LYMPHOCYTES, Autoantigens, Epitope, Mice, TRANSGENIC NOD MICE, 0302 clinical medicine, POTENTIAL CLINICAL-RELEVANCE, Cytotoxic T cell, Child, Cation Transport Proteins, 0303 health sciences, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, ELISPOT, 3. Good health, Child, Preschool, Female, Adult, Adolescent, Population, Mice, Transgenic, PERIPHERAL-BLOOD, Young Adult, 03 medical and health sciences, AGE, Antigen, HLA-A2 Antigen, Internal Medicine, medicine, Animals, Humans, education, Autoantibodies, 030304 developmental biology, Type 1 diabetes, business.industry, Autoantibody, medicine.disease, ZINC TRANSPORTER 8, LONG, Diabetes Mellitus, Type 1, ANTIBODIES, Immunology, Immunology and Transplantation, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, CD8, RESPONSES, 030215 immunology |
| الوصف: | Type 1 diabetes results from the destruction of β-cells by an autoimmune T-cell response assisted by antigen-presenting B cells producing autoantibodies. CD8+ T-cell responses against islet cell antigens, thought to play a central role in diabetes pathogenesis, can be monitored using enzyme-linked immunosorbent spot (ELISpot) assays. However, such assays have been applied to monitoring of adult patients only, leaving aside the large and increasing pediatric patient population. The objective of this study was twofold: 1) to develop a CD8+ T-cell interferon-γ ELISpot assay for pediatric patients and 2) to determine whether zinc transporter 8 (ZnT8), a recently described target of autoantibodies in a majority of patients, is also recognized by autoreactive CD8+ T cells. Using DNA immunization of humanized mice, we identified nine HLA-A2–restricted ZnT8 epitopes. Among 36 HLA-A2+ children with diabetes, 29 responded to ZnT8 epitopes, whereas only 3 of 16 HLA-A2+ control patients and 0 of 17 HLA-A2− control patients responded. Some single ZnT8 epitopes performed as well as the group of epitopes in discriminating between patients and control individuals. Thus, ZnT8 is a major CD8+ T-cell autoantigen, and ELISpot assays display similar performance in adult and pediatric type 1 diabetes. |
| تدمد: | 1939-327X 0012-1797 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a3d0d4fb27bb983dffbf199765b0e712Test https://doi.org/10.2337/db12-0071Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a3d0d4fb27bb983dffbf199765b0e712 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1939327X 00121797 |
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