Suppression of lymphokine-activated killer induction by neutrophils.
Peripheral blood polymorphonuclear neutrophils (PMN) suppressed the induction of PBL lymphokine-activated killer (LAK) function by rIL-2 in vitro. The suppression depended on the concentration of PMN in the IL-2 culture, and required intact PMN. However, PMN did not require treatment with immunoregulators such as IL-2, LPS, or TNF to express the suppressive activity, and no direct contact with PBL was needed for the suppression. Addition of anti-TNF antibodies had no effect on the suppression, suggesting that no endogenous TNF in the culture was involved in the suppression. PMN did not inhibit LAK function by preventing utilization of IL-2 by PBL or by selective depletion of NKH-1+ cells which constitute the majority of LAK precursors in PBL. The suppression was reversed by superoxide dismutase but not by catalase, suggesting that superoxide anion, not hydrogen peroxide, was involved in the suppression. No other suppressive factor was detectable in PMN culture supernates. Our results of PMN regulating LAK induction in vitro suggest that PMN may have a role in determining the outcome of immunotherapy with IL-2 in vivo.
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Armand Hammer Laboratory, John Wayne Cancer Clinic, Los Angeles, CA.
Kim
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D001667:Binding, Competitive; D002470:Cell Survival; D002474:Cell-Free System; D003602:Cytotoxicity, Immunologic; D004247:DNA / Q000096:biosynthesis; D005609:Free Radicals; D006801:Humans; D007165:Immunosuppression Therapy; D007376:Interleukin-2; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D013491:Suppressor Factors, Immunologic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism
D005609:Free Radicals; D007376:Interleukin-2; D013491:Suppressor Factors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D004247:DNA