[HTML][HTML] Highly purified Th17 cells from BDC2. 5NOD mice convert into Th1-like cells in NOD/SCID recipient mice
D Bending, H De La Peña, M Veldhoen… - The Journal of …, 2009 - Am Soc Clin Investig
The Journal of clinical investigation, 2009•Am Soc Clin Investig
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 …
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 …
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.
The Journal of Clinical Investigation