Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 119, Issue 3, Pages 565-572Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI37865
Keywords
-
Categories
Funding
- Wellcome Trust
- Biotechnology and Biological Sciences Research Council (BBSRC).
Ask authors/readers for more resources
Th17 cells are involved in. the pathogenesis of many autoimmune diseases, but it is not clear whether they play a pathogenic role in type I 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-gamma-specific antibody. This result suggested a major role of Th1 cells in the induction of disease in this model of type I 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-gamma at the time of transfer, rapidly converted to secrete IFN-gamma in the NOD/SCID recipients. Purified Th17 cells also upregulated Tbet and secreted IFN-gamma 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available