Prevention of type I diabetes transfer by glutamic acid decarboxylase 65 peptide 206-220-specific T cells
| Autor: | Kristin V. Tarbell, Tibor Warganich, Seon-Kyeong Kim, Maija Sanna, Mark Lee, Mary Vadeboncoeur, Mark M. Davis, Hugh O. McDevitt |
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| Rok vydání: | 2004 |
| Předmět: |
endocrine system
endocrine system diseases T-Lymphocytes T cell Receptors Antigen T-Cell Epitopes T-Lymphocyte Mice Transgenic Biology Lymphocyte Activation Immunotherapy Adoptive Interferon-gamma Mice Interleukin 21 Mice Inbred NOD medicine Animals Cytotoxic T cell Genetic Predisposition to Disease Amino Acid Sequence IL-2 receptor Antigen-presenting cell Cells Cultured NOD mice Multidisciplinary Glutamate Decarboxylase Biological Sciences medicine.disease Natural killer T cell Peptide Fragments Interleukin-10 Diabetes Mellitus Type 1 Glucose medicine.anatomical_structure CD4 Antigens Immunology Female Insulitis |
| Zdroj: | Proceedings of the National Academy of Sciences. 101:14204-14209 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0405500101 |
| Popis: | Glutamic acid decarboxylase (GAD) 65 is one of the major pancreatic antigens targeted by self-reactive T cells in type I diabetes mellitus. T cells specific for GAD65 are among the first to enter inflamed islets and may be important for the initiation of autoimmune diabetes. However, we previously reported that nonobese diabetic (NOD) mice transgenic for a T cell antigen receptor (TCR) specific for one of the immunodominant epitopes of GAD65, peptide 286-300 (G286), are protected from insulitis and diabetes. To examine whether other GAD65-reactive T cells share this phenotype, we have generated TCR transgenic NOD mice for a second immunodominant epitope of GAD65, peptide 206-220 (G206). As in G286 mice, G206 mice do not develop islet inflammation or diabetes. When adoptively transferred along with diabetogenic T cells, activated G206 T cells significantly delayed the onset of diabetes in NOD.scidrecipients. Both G206 and G286 T cells produce immunoregulatory cytokines IFN-γ and IL-10 at low levels when activated by cognate antigens. These data suggest that GAD65-specific T cells may play a protective role in diabetes pathogenesis by regulating pathogenic T cell responses. A better understanding of the functions of autoreactive T cells in type I diabetes will be necessary for choosing desirable targets for immunotherapy. |
| Databáze: | OpenAIRE |
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