Cassatella M A, Trinchieri G, Hassan N F, Hartman L, Sorio C, Berton G
Institute of General Pathology, University of Verona, Italy.
Immunology. 1992 May;76(1):55-9.
Tumour necrosis factor (TNF) and interferon-gamma (IFN-gamma) induce differentiation of human myeloid cell lines along the monocytic lineage. In this study we investigated the effects of TNF and IFN-gamma on the expression of the CD4 protein and messenger RNA (mRNA) in the two myeloid cell lines, ML3 and HL-60. We observed that CD4 antigen expression on ML3 cells is almost undetectable and that TNF and IFN-gamma induced CD4 antigen expression on these cells. HL-60 cells express surface CD4 antigen at high density and treatment with TNF and IFN-gamma caused a decrease of CD4 expression. We also investigated the expression of CD4 mRNA in ML3 and HL-60 cells. ML3 constitutively express, albeit at low levels, CD4 mRNA. TNF induced CD4 mRNA in ML3 cells and IFN-gamma synergistically potentiated the effect of TNF, thus indicating that the enhanced expression of the CD4 protein on ML3 cells is due, at least in part, to an enhanced accumulation of the CD4 mRNA. CD4 mRNA is constitutively expressed in HL-60 cells at high levels. TNF and IFN-gamma, alone or in combination, did not cause any significant change of CD4 mRNA expression in HL-60 cells, thus indicating that decrease of surface CD4, which accompanies differentiation with these cytokines, is likely due to alterations of the CD4 protein synthesis and/or transport to the plasma membrane. These results provide evidence that myeloid cell lines are heterogeneous in expression of CD4, and that in ML3 cells, which constitutively express low levels of CD4 mRNA and undetectable amounts of surface CD4, the predominant effect of the two cytokines is to induce both CD4 mRNA and protein.
肿瘤坏死因子（TNF）和干扰素-γ（IFN-γ）可诱导人髓系细胞系沿单核细胞谱系分化。在本研究中，我们调查了TNF和IFN-γ对两种髓系细胞系ML3和HL-60中CD4蛋白及信使核糖核酸（mRNA）表达的影响。我们观察到ML3细胞上几乎检测不到CD4抗原表达，而TNF和IFN-γ可诱导这些细胞表达CD4抗原。HL-60细胞高密度表达表面CD4抗原，用TNF和IFN-γ处理会导致CD4表达下降。我们还研究了ML3和HL-60细胞中CD4 mRNA的表达。ML3组成性表达CD4 mRNA，尽管水平较低。TNF可诱导ML3细胞表达CD4 mRNA，IFN-γ可协同增强TNF的作用，这表明ML3细胞上CD4蛋白表达增强至少部分是由于CD4 mRNA积累增加所致。HL-60细胞中CD4 mRNA高水平组成性表达。TNF和IFN-γ单独或联合使用均未引起HL-60细胞中CD4 mRNA表达的任何显著变化，这表明这些细胞因子诱导分化时伴随的表面CD4下降可能是由于CD4蛋白合成和/或转运至质膜的改变所致。这些结果证明髓系细胞系在CD4表达上具有异质性，并且在组成性表达低水平CD4 mRNA且表面CD4检测不到的ML3细胞中，这两种细胞因子的主要作用是诱导CD4 mRNA和蛋白表达。
