CC CHEMOKINES INDUCE THE GENERATION OF KILLER-CELLS FROM CD56(+) CELLS

We describe here that members of the CC chemokines exhibit biological activities other than chemotaxis. Macrophage inflammatory protein (MIP )-1 alpha, MIP-1 beta monocyte chemoattractant protein-1 and RANTES, b ut not interleukin (IL)-8. induce the generation of cytolytic cells, d esignated here as CHAK (CC chemokine-activated killer) cells to distin guish them from IL-2-activated (LAK) cells. Like IL-2, CC chemokines. can induce the proliferation and activation of killer cells. While inc ubating CC chemokines with CD4(+) or CD8(+) cells did not generate CHA K activity, all CC chemokines were capable of inducing CHAK activity u pon incubating with CD56(+) cells, suggesting that the primary effecte rs are NK cells. However. the presence of other cell types, such as CD 4(+) or CD8(+), are necessary to induce the proliferation of CD56(+) c ells. Confirming the involvement of T cell-derived factors in inducing the proliferation of these cells, anti-IL-2 and anti-interferon-gamma , but not anti-IL-1 beta, anti-tumor necrosis factor-alpha. anti-IL-8, or anti-granulocyte/monocyte-colony-stimulating factor inhibited RANT ES-induced proliferation of nylon wool column nonadherent cells. Our r esults may have important clinical applications for the utilization of CHAK cells in the treatment of cancer and immunodeficient patients.