Exacerbation of Collagen-Induced Arthritis by Oligoclonal, IL-17-Producing γδ T Cells

Abstract

Murine γδ T cell subsets, defined by their Vγ chain usage, have been shown in various disease models to have distinct functional roles. In this study, we examined the responses of the two main peripheral γδ T cell subsets, Vγ1+ and Vγ4+ cells, during collagen-induced arthritis (CIA), a mouse model that shares many hallmarks with human rheumatoid arthritis. We found that whereas both subsets increased in number, only the Vγ4+ cells became activated. Surprisingly, these Vγ4+ cells appeared to be Ag selected, based on preferential Vγ4/Vδ4 pairing and very limited TCR junctions. Furthermore, in both the draining lymph node and the joints, the vast majority of the Vγ4/Vδ4+ cells produced IL-17, a cytokine that appears to be key in the development of CIA. In fact, the number of IL-17-producing Vγ4+ γδ T cells in the draining lymph nodes was found to be equivalent to the number of CD4+αβ+ Th-17 cells. When mice were depleted of Vγ4+ cells, clinical disease scores were significantly reduced and the incidence of disease was lowered. A decrease in total IgG and IgG2a anti-collagen Abs was also seen. These results suggest that Vγ4/Vδ4+ γδ T cells exacerbate CIA through their production of IL-17.