K/BxN mice develop a spontaneous destructive arthritis driven by T cell dependent anti-glucose-6-phosphate isomerase (GPI) antibody production. In this study, a modified version of the K/BxN model, the KRN-cell transfer model (KRN-CTM), was established to determine the contribution of Th17 cells in the development of chronic arthritis. The transfer of naive KRN T cells into B6.TCR.Cα(-/-)H-2(b/g7) T cell deficient mice induced arthritis by day 10 of transfer. Arthritis progressively developed for a period of up to 14 days following T cell transfer, thereafter the disease severity declined, but did not resolve. Both IL-17A and IFNγ were detected in the recovered T cells from the popliteal lymph nodes and ankles. The transfer of KRN Th17 polarized KRN CD4(+) T cells expressing IL-17A and IFNγ induced arthritis in all B6.TCR.Cα(-/-)H-2(b/g7) mice however the transfer of Th1 polarized KRN CD4(+) T cells expressing IFNγ alone induced disease in only 2/3 of the mice and disease induction was delayed compared to Th17 transfers. Th17 polarized KRN/T-bet(-/-) cells induced arthritis in all mice and surprisingly, IFNγ was produced demonstrating that T-bet expression is not critical for arthritis induction, regardless of the cytokine expression. Neutralization of IFNγ in KRN Th17 transfers resulted in earlier onset of disease while the neutralization of IL-17A delayed disease development. Consistent with K/BxN mice, naive KRN T cell transfers and Th17 polarized KRN/T-bet(-/-) transfers induced anti-GPI IgG(1) dominant responses while KRN Th17 cells induced high levels of IgG(2b). These data demonstrate that Th17 cells can participate in the production of autoantibodies that can induce arthritis.
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