CC chemokines induce the generation of killer cells from CD56+ cells

Abstract

We describe here that members of the CC chemokines exhibit biological activities other than chemotaxis. Macrophage inflammatory protein (MIP)‐1α, MIP‐1β, monocyte chemoattractant protein‐1 and RANTES, but not interleukin (IL)‐8, induce the generation of cytolytic cells, designated here as CHAK (CC chemokine‐activated killer) cells to distinguish them from IL‐2‐activated (LAK) cells. Like IL‐2, CC chemokines can induce the proliferation and activation of killer cells. While incubating CC chemokines with CD4+ or CD8+ cells did not generate CHAK activity, all CC chemokines were capable of inducing CHAK activity upon incubating with CD56+ cells, suggesting that the primary effectors are NK cells. However, the presence of other cell types, such as CD4+ or CD8+, are necessary to induce the proliferation of CD56+ cells. Confirming the involvement of T cell‐derived factors in inducing the proliferation of these cells, anti‐IL‐2 and anti‐interferon‐γ, but not anti‐IL‐1β, anti‐tumor necrosis factor‐α, anti‐IL‐8, or anti‐granulocyte/monocyte‐colony‐stimulating factor inhibited RANTES‐induced proliferation of nylon wool column‐nonadherent cells. Our results may have important clinical applications for the utilization of CHAK cells in the treatment of cancer and immunodeficient patients.