Presence of Diabetes-Inhibiting, Glutamic Acid Decarboxylase-Specific, IL-10-Dependent, Regulatory T Cells in Naive Nonobese Diabetic Mice
| Autor: | Todd M. Brusko, Mark A. Atkinson, Cyndi Chen, Wen-Hui Lee, Chih-Pin Liu, Sylvaine You |
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| Rok vydání: | 2004 |
| Předmět: |
CD4-Positive T-Lymphocytes
Immunology Epitopes T-Lymphocyte Cell Separation Mice SCID Biology Prediabetic State Mice Interleukin 21 Mice Inbred NOD T-Lymphocyte Subsets Animals Immunology and Allergy Cytotoxic T cell IL-2 receptor Antigen-presenting cell NOD mice CD40 Glutamate Decarboxylase Immunodominant Epitopes Natural killer T cell Adoptive Transfer Molecular biology Peptide Fragments Interleukin-10 Diabetes Mellitus Type 1 Interleukin 12 biology.protein Cytokines Female Spleen |
| Zdroj: | The Journal of Immunology. 173:6777-6785 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.173.11.6777 |
| Popis: | Immunization of NOD mice with autoantigens such as glutamic acid decarboxylase (GAD) 221–235 peptide (p221) can induce Ag-specific CD4+ T regulatory (Tr) cells. However, it is unclear whether these Tr cells acquire their regulatory capacity due to immunization or whether they are constitutively harbored in unimmunized naive mice. To address this question, we used an I-Ag7 tetramer to isolate p221-specific T cells from naive NOD mice (N221+ cells) after peptide-specific in vitro expansion. The N221+ T cells produced IFN-γ and IL-10, but very little IL-4, in response to p221 stimulation. These T cells could function as regulatory cells and inhibit in vitro proliferation of diabetogenic BDC2.5 cells. This suppressive activity was cell contact-independent and was abrogated by Abs to IL-10 or IL-10R. Interestingly, IL-2 produced by other T cells present in the cell culture induced unactivated N221+ T cells to exhibit regulatory activities involving production of IL-10. In vivo, N221+ cells inhibited diabetes development when cotransferred with NOD splenocytes into NOD/scid recipients. Together, these results demonstrate that p221-specific IL-10-dependent Tr cells, including Tr type 1 cells, are present in naive NOD mice. The use of spontaneously arising populations of GAD peptide-specific Tr cells may represent a promising immunotherapeutic approach for preventing type 1 diabetes. |
| Databáze: | OpenAIRE |
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