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, 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-gamma, but not anti-IL-1 beta, anti-tumor necrosis factor-alpha, 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.
Maghazachi
A A
AA
Department of Anatomy, University of Oslo, Norway.
Al-Aoukaty
A
A
Schall
T J
TJ
D019002:CD56 Antigen / Q000032:analysis*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D018932:Chemokine CCL2 / Q000494:pharmacology; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000494:pharmacology; D018925:Chemokines / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D004915:Leukemia, Erythroblastic, Acute; D008213:Lymphocyte Activation / Q000187:drug effects; D019402:Macrophage Inflammatory Proteins; D015846:Monokines / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D019002:CD56 Antigen; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D019402:Macrophage Inflammatory Proteins; D015846:Monokines