Exacerbation of collagen-induced arthritis by oligoclonal, IL-17-producing γδ T cells

Murine gamma delta T cell subsets, defined by their V gamma 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 gamma delta T cell subsets, V gamma 1(+) and V gamma 4(+) 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 V gamma 4(+) cells became activated. Surprisingly, these V gamma 4(+) cells appeared to be Ag selected, based on preferential V gamma 4/V delta 4 pairing and very limited TCR junctions. Furthermore, in both the draining lymph node and the joints, the vast majority of the V gamma 4/V delta 4(+) cells produced IL-17, a cytokine that appears to be key in the development of CIA. In fact, the number of IL-17-producing V gamma 4(+) gamma delta T cells in the draining lymph nodes was found to be equivalent to the number of CD4(+) alpha beta(+) Th-17 cells. When mice were depleted of V gamma 4(+) 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 V gamma 4/V delta 4(+) gamma delta T cells exacerbate CIA through their production of IL-17.