Treatment with recombinant IFN-gamma decreases cell surface CD4 levels on peripheral blood monocytes and on myelomonocyte cell lines.
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.
Faltynek
C R
CR
Biological Carcinogenesis Development Program, National Cancer Institute, Frederick, MD 21701.
Finch
L R
LR
Miller
P
P
Overton
W R
WR
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
D003470:Culture Media; D006133:Growth Substances; D008222:Lymphokines; D015728:Receptors, HIV; D011991:Receptors, Virus; D011994:Recombinant Proteins; D007371:Interferon-gamma