Modulation of human natural killer cell function by cytokines and rheumatic disease.
The activity of natural killer (NK) cells can be modified by a number of factors that either increase or suppress cytotoxicity. We have investigated in detail the cytokine induced killing of a NK resistant renal carcinoma cell line Cur by human NK cells. Preincubation of peripheral blood mononuclear cells with interferon alpha (IFN alpha), interleukin 2 (Il-2), interleukin 1 (Il-1) and tumor necrosis factor alpha greatly increased the rate and magnitude of Cur killing. Positively selected CD16 (+) cells were found to respond to cytokine stimulation and to mediate Cur killing. The effects of Il-2 and IFNa could be upregulated by costimulation of effector cells with Il-1 or TNF alpha. It was shown that TNF alpha induced Il-2 receptor expression on CD16(+) cells alone and even more in combination with Il-2. Studies of NK cell function in various rheumatic diseases revealed reduced NK cytotoxicity in peripheral blood and synovial fluid (SF), both in rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA). By contrast, normal NK function was found in patients with ankylosing spondylitis (AS) and psoriatic arthritis. A discordance with regard to the percentage of Leu 7 positive mononuclear cells and NK function in peripheral blood and SF was demonstrated. Minimal expression of Leu 7 positive cells and cytotoxicity was present in synovial membranes. NK function in rheumatic disease was largely independent of drug therapy. Natural killer (NK) cells are a subset of lymphocytes that mediate spontaneous cytotoxicity against certain tumor and virus infected cells without any known prior sensitation.(ABSTRACT TRUNCATED AT 250 WORDS)
Ostensen
M
M
Oslo Sanitetsforening Rheumatism Hospital, Norway.
Førre
O
O
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001685:Biological Factors / Q000502:physiology*; D001696:Biomechanical Phenomena; D016207:Cytokines; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000502:physiology*; D012216:Rheumatic Diseases / Q000473:pathology / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D001685:Biological Factors; D016207:Cytokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha