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Highly purified Th17 cells from BDC2.5NOD mice convert into Th1-like cells in NOD/SCID recipient mice
David Bending, … , Brigitta Stockinger, Anne Cooke
David Bending, … , Brigitta Stockinger, Anne Cooke
Published February 2, 2009
Citation Information: J Clin Invest. 2009;119(3):565-572. https://doi.org/10.1172/JCI37865.
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Research Article Immunology

Highly purified Th17 cells from BDC2.5NOD mice convert into Th1-like cells in NOD/SCID recipient mice

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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.

Authors

David Bending, Hugo De La Peña, Marc Veldhoen, Jenny M. Phillips, Catherine Uyttenhove, Brigitta Stockinger, Anne Cooke

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Figure 1

Th17 cells cause diabetes in NOD/SCID mice.

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Th17 cells cause diabetes in NOD/SCID mice.
(A) Intracellular staining f...
(A) Intracellular staining for IL-17 and IFN-γ of polarized Th17 or Th1 BDC2.5 cells was performed on day 4 of culture. Cells were transferred into NOD/SCID recipients and incidence of diabetes for Th1 (n = 5) (filled symbols) and Th17 (n = 5) (open symbols) transfer is shown. (B) Intracellular staining of CD4+Vβ4+ T cells in the PLNs on day 8 after transfer is shown. (C) Intracellular staining was performed as in A, followed by transfer into antibody-treated NOD/SCID recipients. Th17 were transferred into isotype control–treated (n = 4) (open diamonds) or anti–IFN-γ–treated (n = 5) (filled squares) hosts. Th1 were transferred into isotype-treated (n = 4) (open triangles) or anti–IFN-γ–treated (n = 5) (filled diamonds) hosts. (D) Representative FACS plots of CD4+Vβ4+ T cells in PLNs and pancreata of isotype–treated (left panels) or anti–IFN-γ–treated (right panels) hosts 10 days after transfer. Numbers indicate the percentage of cells in each quadrant.

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