Interleukin-7 selectively enhances natural kill cytotoxicity mediated by the CD56bright natural killer subpopulation.
Both the CD56bright and CD56dim NK cell subpopulation mediate non-major histocompatibility complex-restricted cytolysis of NK-sensitive tumor cell lines, and IL-2-dependent augmentation of cytolysis and proliferation of CD56bright and CD56dim NK cells was recently reported. We investigated the effects of IL-7 and IL-6 on the killing mediated by these cells to determine whether other cytokines besides IL-2 regulate their activity. IL-7 increased the cytotoxicity in only the CD56bright NK cell population. The effect of IL-7 varied from donor to donor but was comparable to that of IL-2. Furthermore, IL-7 was found to induce lymphokine-activated killer (LAK) cell generation primarily in the CD56bright cells. CD56bright NK cells also proliferated in response to IL-7, but only weakly in comparison with IL-2. In contrast to the results with CD56bright NK cells, IL-7 had little effect on the CD56dim subset. However, IL-2 enhanced NK cytotoxicity, induced LAK activity, and caused proliferation of these cells. An anti-IL-2 antibody did not inhibit the IL-7-induced increase in CD56bright cytotoxicity, suggesting that IL-7 acted independently of IL-2. However, the IL-7 effect on CD56bright NK cell cytotoxicity was partially inhibited by anti-CD2, anti-CD11a, and anti-CD18 antibodies and almost completely abrogated by a combination of anti-CD2 and anti-CD11a. These data suggest that cell adhesion molecules (CAM) play a role in the regulation of IL-7-induced CD56bright NK cell cytolysis. In contrast to IL-7-mediated effects, IL-6 alone had no effect on CD56+ NK cell cytotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
Dadmarz
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Division of Surgical Oncology, Center for Health Sciences, University of California-Los Angeles School of Medicine.
Bockstoce
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DC
Golub
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SH
D015703:Antigens, CD / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D019002:CD56 Antigen; D015815:Cell Adhesion Molecules / Q000276:immunology; D002455:Cell Division; D003602:Cytotoxicity, Immunologic; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000037:antagonists & inhibitors; D015851:Interleukin-7 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D009500:Neutralization Tests; D014407:Tumor Cells, Cultured / Q000276:immunology
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D019002:CD56 Antigen; D015815:Cell Adhesion Molecules; D007376:Interleukin-2; D015851:Interleukin-7