Feldman M, Howell D, Fitzgerald-Bocarsly P
Department of Laboratory Medicine and Pathology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark 07103.
J Leukoc Biol. 1992 Nov;52(5):473-82. doi: 10.1002/jlb.52.5.473.
Human natural killer (NK) cells require an HLA-DR+ accessory cell (AC) population to lyse herpes simplex virus-type 1 (HSV-1)-infected fibroblasts (HSV-Fs) but not K562 target cells. It has been postulated that ACs may function by producing interferon-alpha (IFN-alpha), which stimulates NK cells. Using a sequential enrichment protocol, ACs were found to coenrich with the interferon-producing cells (IPCs). Treatment of the ACs with a protein synthesis inhibitor, emetine, inhibited both their IFN production and AC function, results that support a central role for IFN in AC activity. In contrast, when the arginine analogue canavanine was added to NK assays, no IFN-alpha was produced and NK(HSV-Fs) activity was only partially inhibited. Consistent with IFN-independent AC function, treatment with either polyclonal sheep or bovine anti-IFN-alpha neutralized all the IFN-alpha produced during the NK assays but caused either no or partial reduction of NK(HSV-Fs) activity, respectively. However, when limiting numbers of ACs were used, the bovine antiserum neutralized both IFN-alpha and NK(HSV-Fs) activity. We further found that HLA-DR+ cells are required for cell clustering, suggesting a role for cell contact. Finally, fixation of activated ACs prevented the accessory function. Together, these results demonstrate that ACs can provide help to NK cells in both IFN-alpha-dependent and -independent manners.
人类自然杀伤（NK）细胞需要HLA - DR⁺辅助细胞（AC）群体来裂解单纯疱疹病毒1型（HSV - 1）感染的成纤维细胞（HSV - Fs），但不需要裂解K562靶细胞。据推测，AC可能通过产生刺激NK细胞的α干扰素（IFN - α）发挥作用。使用连续富集方案，发现AC与产生干扰素的细胞（IPC）共同富集。用蛋白质合成抑制剂依米丁处理AC，可抑制其IFN产生和AC功能，这些结果支持IFN在AC活性中起核心作用。相反，当将精氨酸类似物刀豆氨酸添加到NK测定中时，未产生IFN - α，且NK（HSV - Fs）活性仅被部分抑制。与不依赖IFN的AC功能一致，用多克隆绵羊或牛抗IFN - α处理可中和NK测定过程中产生的所有IFN - α，但分别导致NK（HSV - Fs）活性无降低或部分降低。然而，当使用有限数量的AC时，牛抗血清可中和IFN - α和NK（HSV - Fs）活性。我们进一步发现，细胞聚集需要HLA - DR⁺细胞，提示细胞接触起作用。最后，固定活化的AC可阻止辅助功能。总之，这些结果表明，AC可以通过依赖IFN - α和不依赖IFN - α的方式为NK细胞提供帮助。
