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

TLDR

Th17 cells are implicated in many autoimmune diseases, yet their pathogenic role in type 1 diabetes remains uncertain. The study examined whether islet‑antigen–specific mouse Th17 cells could induce diabetes when adoptively transferred into NOD/SCID mice. Transfer of highly purified Th17 cells from BDC2.5 transgenic mice induced diabetes in NOD/SCID recipients at rates comparable to Th1 cells, but the Th17 cells rapidly converted to IFN‑γ–secreting Th1‑like cells, and neutralizing IL‑17 did not prevent disease while neutralizing IFN‑γ blocked Th1‑cell–induced diabetes, underscoring Th1 cells’ central role and Th17 plasticity.

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.