Arenzana-Seisdedos F, Mogensen S C, Vuillier F, Fiers W, Virelizier J L
Laboratoire d'Immunologie Virale, Institut Pasteur, Paris, France.
Proc Natl Acad Sci U S A. 1988 Aug;85(16):6087-91. doi: 10.1073/pnas.85.16.6087.
Recombinant interferon-gamma (IFN-gamma) induced HLA-DR gene expression in both U937 and THP-1 human monocytic cell lines, although the former was only very weakly inducible. Combination of recombinant tumor necrosis factor (TNF) and IFN-gamma resulted in a synergistic enhancement of DR mRNA and protein induction in both cell lines. TNF alone increased the constitutive expression of the DR gene in THP-1 cells. In the HLA class II-negative U937 cells, TNF used alone was not able to induce DR gene expression. Such a negative result was not due to a lack of TNF receptor expression in U937 cells, since TNF clearly induced HLA class I and TNF gene expression in this cell line. THP-1, but not U937, cells secreted TNF under the influence of IFN-gamma. Neutralization of TNF by a specific antibody decreased IFN-gamma-induced DR antigen expression in THP-1 cultures. These observations indicate that TNF is not able to directly induce DR gene expression, but rather amplifies ongoing expression of this gene, whether constitutive or induced by IFN-gamma. In the two cell lines tested, the level of DR inducibility under the influence of IFN-gamma used alone depended on a different inducibility of TNF secretion by IFN-gamma. Altogether, our observations indicate that TNF, whether exogenous or endogenously produced under the influence of IFN-gamma, amplifies DR gene expression in monocytes, a phenomenon that may provide to such antigen-presenting cells a selective sensitivity to the DR-inducing effects of IFN-gamma.
重组干扰素 -γ（IFN -γ）可诱导U937和THP -1人单核细胞系中的HLA -DR基因表达，尽管前者的诱导性非常弱。重组肿瘤坏死因子（TNF）与IFN -γ联合使用可导致两种细胞系中DR mRNA和蛋白诱导的协同增强。单独使用TNF可增加THP -1细胞中DR基因的组成性表达。在HLA II类阴性的U937细胞中，单独使用TNF不能诱导DR基因表达。这样的阴性结果并非由于U937细胞中缺乏TNF受体表达，因为TNF能明显诱导该细胞系中的HLA I类和TNF基因表达。THP -1细胞而非U937细胞在IFN -γ的影响下分泌TNF。用特异性抗体中和TNF可降低THP -1培养物中IFN -γ诱导的DR抗原表达。这些观察结果表明，TNF不能直接诱导DR基因表达，而是放大该基因的持续表达，无论其是组成性表达还是由IFN -γ诱导的表达。在测试的两种细胞系中，单独使用IFN -γ时DR的诱导水平取决于IFN -γ诱导TNF分泌的不同诱导性。总之，我们的观察结果表明，TNF无论是外源性的还是在IFN -γ影响下内源性产生的，都会放大单核细胞中DR基因的表达，这一现象可能使此类抗原呈递细胞对IFN -γ的DR诱导作用具有选择性敏感性。
