Highly purified Th17 cells from BDC2.5NOD mice convert into Th1-like cells in NOD/SCID recipient mice
Research output: Contribution to journal › Article › peer-review
Colleges, School and Institutes
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.
|Number of pages||8|
|Journal||Journal of Clinical Investigation|
|Publication status||Published - Mar 2009|
- 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