IL-17 is produced mainly by activated CD4+ T cells, especially for Th1/Th0 cells, not the Th2 phenotype [26]. However, it can also be produced by CD8+ T cells via an IL-23 triggering mechanism in Gram-negative pulmonary infection [14]. In addition, IL-17 production was significantly augmented by T cells recognizing type II collagen in a collagen-induced arthritis model [27]. A complex interaction between cells in inflamed RA joints might produce a variety of proinflammatory cytokines and chemokines, which also activate other cells in the joints. For example, IL-17 stimulates rheumatoid synoviocytes to secrete several cytokines such as IL-6, IL-8 and tumor necrosis factor-stimulated gene 6 as well as prostaglandin E2 in vitro [12,28,29]. There are as yet few data available on the agents that stimulate IL-17 production in RA, although some cytokines (IL-15 and IL-23) have been known to regulate IL-17 production [13,14]. We therefore investigated the in vitro production of IL-17 in RA PBMC responding to a variety of cytokines/chemokines and mitogens as well as T cell receptor (TCR) ligation using anti-CD3/anti-CD28. Our studies demonstrated that IL-15 and MCP-1 as well as TCR ligation significantly increased the production of IL-17 in RA PBMC. Adding IL-15 or MCP-1 to TCR ligation augmented IL-17 production more markedly. In contrast, IL-1 and TNF-α, which are known to have proinflammatory properties and to be increased in RA joints, did not affect IL-17 production. Our data were consistent with a recent report that IL-15 triggered in vitro IL-17 production in PBMC, but TNF-α did not do so [13]. Although there were no data that MCP-1 directly induces T cell activation, it might exert effects indirectly on T cells through the activation of monocytes/macrophages in PBMC cultures. As reported for normal individuals [25], T cell activation through anti-CD3/anti-CD28 also increases IL-17 induction in RA PBMC.