Characterization of human IFN-gamma response using somatic cell hybrids of hematopoietic and nonhematopoietic origin.
A panel of 27 rodent-human somatic cell hybrids composed of cells of hematopoietic (nonadherent cells) and nonhematopoietic origin (adherent cells) was used to identify the chromosomes involved in the biological response to human IFN-gamma (Hu-IFN-gamma). We found that the stimulation of class-I histocompatibility antigen expression correlates with the presence of human chromosomes 6 and 21 in adherent cell hybrids, while human chromosome 6 alone is sufficient in nonadherent hybrids. Scatchard analysis of the binding of radiolabeled Hu-IFN-gamma to nonadherent cell hybrids gave a Kd value similar to that found on human cell lines. Induction of a reporter gene placed under the transcriptional control of the interferon responsive sequence (IRS) in adherent cell hybrids requires both chromosomes 6 and 21. The antiviral protection by Hu-IFN-gamma in adherent cell hybrids was reached at physiological doses (2 units/ml) when human chromosomes 6 and 21 were present, while higher doses of Hu-IFN-gamma (5000 units/ml) were required for hybrids lacking chromosome 21. Thus, we demonstrate that differences exit in the response to Hu-IFN-gamma depending on the origin of the cell type.
Bono
M R
MR
Institut Pasteur-INSERM U.276.
Benech
P
P
Couillin
P
P
Alcaide-Loridan
C
C
Grisard
M C
MC
Jouin
H
H
Fischer
D G
DG
Fellous
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002460:Cell Line; D002891:Chromosomes, Human, Pair 21; D002896:Chromosomes, Human, Pair 6; D004351:Drug Resistance / Q000235:genetics; D005455:Fluorescent Antibody Technique; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D004854:Herpesvirus 4, Human; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D006822:Hybrid Cells; D007371:Interferon-gamma / Q000494:pharmacology*; D014162:Transfection; D014721:Vesicular stomatitis Indiana virus
D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma