NATURAL-KILLER (NK) CELL-DERIVED HEMATOPOIETIC COLONY-INHIBITING ACTIVITY AND NK CYTO-TOXIC FACTOR - RELATIONSHIP WITH TUMOR NECROSIS FACTOR AND SYNERGISM WITH IMMUNE INTERFERON
NATURAL-KILLER (NK) CELL-DERIVED HEMATOPOIETIC COLONY-INHIBITING ACTIVITY AND NK CYTO-TOXIC FACTOR - RELATIONSHIP WITH TUMOR NECROSIS FACTOR AND SYNERGISM WITH IMMUNE INTERFERON
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DOI：
10.1084/jem.162.5.1512
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发表时间：
1985-01-01
影响因子：
15.3
通讯作者：
TRINCHIERI, G
中科院分区：
文献类型：
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作者：
DEGLIANTONI, G;MURPHY, M;TRINCHIERI, G
我们表征了人外周血淋巴细胞 (PBL) 与 NK 敏感靶细胞系培养物上清液中产生的自然杀伤 (NK) 细胞集落抑制活性 (CIA)，并研究了其与 NK 细胞衍生的细胞毒因子 (NKCF) 的关系。使用针对 NK 细胞或其他淋巴细胞群的特异性单克隆抗体 (mAb)，我们明确地将 NK 细胞确定为唯一能够产生 NKCF 和 NK-CIA 的 PBL 子集。我们提供的功能和生化数据表明 NKCF 和 NK-CIA 代表相同的分子：（a）不同 PBL 子集独立产生的上清液中 NKCF 和 NK-CIA 的数量之间存在高度显着的正相关； (b) NK-CIA和NKCF均由PBL与NK敏感细胞系和HLA-DR+骨髓细胞培养诱导，但不与NK不敏感细胞系一起培养； (c) NKCF和NK-CIA均被相同细胞系或骨髓细胞类型吸收； (d) 两种活性在相同的凝胶过滤级分中共洗脱； (e) D-甘露糖-6-磷酸阻断 NKCF 和 NK-CIA 活性，并阻止 K562 细胞吸收它们； (f) NLKCF 和 NK-CIA 活性在 37°C 2 天后消失。 C.含有NK-CIA的制剂缺乏抗病毒活性，并且抗干扰素（抗-IFN）抗体不会阻断NK-CIA的抑制活性。 NK-CIA对第14天（早期）粒细胞和巨噬细胞集落形成单位（CFU-GM）的作用与IFN-γ具有协同作用，并且这种协同作用在第7天（晚期）CFU-GM生长中也很明显。 NK-CIA 和 IFN-.gamma 的组合。抑制晚期 CFU-GM，两种淋巴因子的浓度单独使用时完全无效。 NK-CIA 和 IFN-.α 之间没有协同作用。或-.beta。观察到，由于这两种 IFN 类型对晚期 CFU-GM 具有直接抑制作用。肿瘤坏死因子 (TNF) 特异性抗体（而非淋巴毒素特异性抗体）可抑制 NK 细胞上清液中的 NK-CIA 和 NKCF 活性。重组TNF在与上清液中存在的L-929细胞的细胞毒活性相对应的浓度范围内介导NKCF和NK-CIA活性。总之，我们的数据表明，负责 NK 细胞上清液对 NK 敏感细胞系的细胞毒性作用和相同上清液对骨髓细胞的细胞毒性或细胞抑制作用的分子是相同的，并且这些分子在抗原性、功能性和生物化学性上与人单核细胞和骨髓细胞系产生的 TNF 相似或相同。
We characterize the natural killer (NK) cell colony-inhibiting activity (CIA) produced in supernatants from cultures of human peripheral blood lymphocytes (PBL) with NK-sensitive target cell lines, and study its relationship with NK cell-derived cytotoxic factor (NKCF). Using monoclonal antibodies (mAb) specific for NK cells or other lymphocyte populations, we unambiguously identify NK cells as the only PBL subset able to produce both NKCF and NK-CIA. We present functional and biochemical data suggesting that NKCF and NK-CIA represent the same molecule: (a) a highly significant positive correlation exists between the quantity of NKCF and NK-CIA in supernatants independently produced by different PBL subsets; (b) both NK-CIA and NKCF are induced by culture of PBL with NK-sensitive, but not with NK-insensitive cell lines, and with HLA-DR+ bone marrow cells; (c) both NKCF and NK-CIA are absorbed on the same cell lines or bone marrow cell types; (d) the two activities coelute in the same gel filtration fractions; (e) D-mannose-6-phosphate blocks both NKCF and NK-CIA activity, and prevents their absorption by K562 cells; and (f) both NLKCF and NK-CIA activity are lost after 2 d at 37.degree. C. The NK-CIA-containing preparations are devoid of antiviral activity, and antiinterferon (anti-IFN) antibodies do not block the inhibitory activity of NK-CIA. The effect of NK-CIA on day 14 (early) colony-forming units of granulocytes and macrophages (CFU-GM) is synergistic with that of IFN-.gamma., and this synergy is also evident on day 7 (late) CFU-GM growth. A combination of NK-CIA and IFN-.gamma. suppresses late CFU-GM, at concentrations of the two lymphokines that are completely ineffective when used independently. No synergy between NK-CIA and IFN-.alpha. or -.beta. was observed, due to a direct inhibitory effect of these two IFN types on late CFU-GM. Antibodies specific for tumor necrosis factor (TNF), but not those specific for lymphotoxins, inhibit both NK-CIA and NKCF activity in the NK cell-derived supernatant. Recombinant TNF, in the range of concentrations corresponding to that of the cytotoxic activity on L-929 cells present in supernatants, mediated both NKCF and NK-CIA activity. Together, our data suggest that the molecules responsible for both the cytotoxic effect of NK cell supernatants on NK-sensitive cell lines and the cytotoxic or cytostatic effect of the same supernatants on bone marrow cells are identical, and that these molecules are antigenically, functionally, and biochemically similar to or identical with the TNF produced by human monocytes and myeloid cell lines.