title: Induction of differentiation of the human myeloid cell line, ML3, by tumour necrosis factor and interferon-gamma is accompanied by enhanced expression of the CD4 protein and messenger RNA.
abstract: 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.
authors.affiliation: Institute of General Pathology, University of Verona, Italy.
authors.forename: M A
authors.initials: MA
authors.lastname: Cassatella
authors.forename: G
authors.initials: G
authors.lastname: Trinchieri
authors.forename: N F
authors.initials: NF
authors.lastname: Hassan
authors.forename: L
authors.initials: L
authors.lastname: Hartman
authors.forename: C
authors.initials: C
authors.lastname: Sorio
authors.forename: G
authors.initials: G
authors.lastname: Berton
mesh_terms: D015152:Blotting, Northern; D015704:CD4 Antigens / Q000032:analysis* / Q000235:genetics; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D007700:Kinetics; D009000:Monocytes / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis*; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma