Abstract
Th17 cells are involved in the pathogenesis of many autoimmune diseases, but it is not clear whether they play a pathogenic role in type 1 diabetes. Here we investigated whether mouse Th17 cells with specificity for an islet antigen can induce diabetes upon transfer into NOD/SCID recipient mice. Induction of diabetes in NOD/SCID mice via adoptive transfer of Th1 cells from BDC2.5 transgenic mice was prevented by treatment of the recipient mice with a neutralizing IFN-γ-specific antibody. This result suggested a major role of Th1 cells in the induction of disease in this model of type 1 diabetes. Nevertheless, transfer of highly purified Th17 cells from BDC2.5 transgenic mice caused diabetes in NOD/SCID recipients with similar rates of onset as in transfer of Th1 cells. However, treatment with neutralizing IL-17-specific antibodies did not prevent disease. Instead, the transferred Th17 cells, completely devoid of IFN-γ at the time of transfer, rapidly converted to secrete IFN-γ in the NOD/SCID recipients. Purified Th17 cells also upregulated Tbet and secreted IFN-γ upon exposure to IL-12 in vitro and in vivo in NOD/SCID recipients. These results indicate substantial plasticity of Th17 commitment toward a Th1-like profile.
Original language | English |
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Pages (from-to) | 565-72 |
Number of pages | 8 |
Journal | Journal of Clinical Investigation |
Volume | 119 |
Issue number | 3 |
DOIs | |
Publication status | Published - Mar 2009 |
Keywords
- Adoptive Transfer
- Animals
- Antibodies, Monoclonal
- Basic Helix-Loop-Helix Transcription Factors
- Blood Glucose
- Cell Differentiation
- Diabetes Mellitus, Type 1
- Down-Regulation
- Gene Expression
- Interferon-gamma
- Interleukin-12
- Interleukin-17
- Lymph Nodes
- Macrophages
- Mice
- Mice, Inbred C57BL
- Mice, Inbred NOD
- Mice, SCID
- Nuclear Receptor Subfamily 1, Group F, Member 3
- Pancreas
- Receptors, Aryl Hydrocarbon
- Receptors, Interleukin
- Receptors, Interleukin-12
- T-Box Domain Proteins
- Th1 Cells
- Th17 Cells
- Up-Regulation
- Xenopus Proteins
- Journal Article
- Research Support, Non-U.S. Gov't