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.