Activated γδ T cells inhibit osteoclast differentiation and resorptive activity in vitro

Extensive evidence suggests that the immune system exerts powerful effects on bone cells, particularly in chronic disease pathologies such as rheumatoid arthritis (RA). The chronic inflammatory state in RA, particularly the excessive production of T cell-derived proinflammatory cytokines such as tumour necrosis factor (TNF)- and interleukin (IL)-17, triggers bone erosions through the increased stimulation of osteoclast formation and activity. While evidence supports a role for IL-17 and TNF- secreted by conventional CD4(+) T cells in RA, recent evidence in animal models of RA have implicated T cells as a major producer of pathogenic IL-17. However, the capacity of T cells to influence osteoclast formation and activity in humans has not yet been investigated widely. To address this issue we investigated the effects of T cells on osteoclast differentiation and resorptive activity. We have demonstrated that anti-CD3/CD28-stimulated T cells or CD4(+) T cells inhibit human osteoclast formation and resorptive activity in vitro. Furthermore, we assessed cytokine production by CD3/CD28-stimulated T cells and observed a lack of IL-17 production, with activated T cells producing abundant interferon (IFN)-. The neutralization of IFN- markedly restored the formation of osteoclasts from precursor cells and the resorptive activity of mature osteoclasts, suggesting that IFN- is the major factor responsible for the inhibitory role of activated T cells on osteoclastogenesis and resorptive activity of mature osteoclasts. Our work therefore provides new insights on the interactions between T cells and osteoclasts in humans.