title: Treatment with recombinant IFN-gamma decreases cell surface CD4 levels on peripheral blood monocytes and on myelomonocyte cell lines.
abstract: The human cell surface protein CD4 is not only an important accessory molecule in the activation of MHC class-II-restricted T cells, but has also been implicated to be a receptor for the human immunodeficiency virus HIV-I on lymphoid and monocytic cells. We have found that a 24-h treatment of the promonocytic leukemia cell line U937 with rIFN-gamma decreases the expression of the CD4 Ag by 50% as measured by cytofluorographic analysis. The decrease in CD4 expression was dependent on the concentration of rIFN-gamma, with maximal effects occurring at 20 to 200 U/ml. The decrease appeared to be due to actual loss of the CD4 molecule from the cell surface rather than masking of a particular epitope, inasmuch as similar results were obtained with the OKT4 and OKT4A antibodies. The effect of rIFN-gamma to decrease CD4 expression was not due to a general loss of cell surface Ag, because the binding of OKM1 and anti-HLe-1 increased after rIFN-gamma treatment. Treatment of rIFN-gamma also decreased cell surface CD4 expression on the promyelocytic leukemia cell line HL-60, and on the monocytic cell line THP-1, although the extent of the decrease was less than on U937 cells. Freshly isolated normal peripheral blood monocytes treated for 48 h with rIFN-gamma bound much less OKT4 or OKT4A antibody than cells incubated in the absence of rIFN-gamma. Moreover, treatment with rIFN-gamma reduced the percentage of peripheral blood monocytes that were positive for the CD4 Ag. In contrast with the decrease in CD4 levels on rIFN-gamma-treated monocytes, treatment with rIFN-gamma had no effect on CD4 levels on peripheral blood T lymphocytes or T cell lines.
authors.affiliation: Biological Carcinogenesis Development Program, National Cancer Institute, Frederick, MD 21701.
authors.forename: C R
authors.initials: CR
authors.lastname: Faltynek
authors.forename: L R
authors.initials: LR
authors.lastname: Finch
authors.forename: P
authors.initials: P
authors.lastname: Miller
authors.forename: W R
authors.initials: WR
authors.lastname: Overton
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003470:Culture Media; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007948:Leukemia, Monocytic, Acute / Q000378:metabolism; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism; D008222:Lymphokines / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D015728:Receptors, HIV; D011991:Receptors, Virus / Q000378:metabolism*; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D003470:Culture Media; D006133:Growth Substances; D008222:Lymphokines; D015728:Receptors, HIV; D011991:Receptors, Virus; D011994:Recombinant Proteins; D007371:Interferon-gamma