Interleukin-15 selectively expands CD57+CD28−CD4+ T cells, which are increased in active rheumatoid arthritis

Proinflammatory cytokines as well as CD4+ T cells play critical roles in the pathogenesis of rheumatoid arthritis (RA). Recently, an increase of CD57+ or CD28−CD4+ T cells was demonstrated in RA, although the mechanism of the increase of these T cells is unclear. In this study, we first examined the relationship between CD57+CD4+ T cells and CD28−CD4+ T cells and found CD57+CD28−CD4+ T cells, but neither CD57+CD28+ nor CD57−CD28+ cells, expanded in the peripheral blood of active RA. In vitro experiments revealed that CD57+CD28−CD4+ T cells selectively expanded in response to IL-15. Furthermore IL-15-stimulated CD57+CD28−CD4+ T cells induced TNF-α production from monocytes. These results suggest that CD57+CD28−CD4+ T cells are involved in the pathogenesis of RA by responding to IL-15.