Differential effects of epidermal growth factor, transforming growth factor-alpha, and vaccinia virus growth factor in the positive regulation of IFN-gamma production.
We have recently shown that epidermal growth factor (EGF) is capable of positive regulation of IFN-gamma production, thus establishing a functional relationship between nonhemopoietic growth factors and the immune system. In order to study this relationship further, EGF and the EGF-related growth factors transforming growth factor-alpha (TGF-alpha) and vaccinia virus growth factor (VGF), which stimulate cellular proliferation via binding to the EGF receptor, were studied for their functional and physicochemical effects on IFN-gamma production. In contrast to the positive signal of purified murine EGF and recombinant human EGF (both at 1 nM), neither synthetic TGF alpha nor recombinant VGF were capable of restoring competence for IFN-gamma production by Th cell-depleted spleen cell cultures. TGF-alpha and VGF, in molar excess, also failed to block the helper signal of EGF for IFN-gamma production. Thus TGF-alpha and VGF failed to functionally compete for the EGF receptor in the murine spleen cell system. Both TGF-alpha and VGF stimulated murine 3T3 cell proliferation at concentrations similar to those of EGF, and thus their failure to provide help for IFN-gamma production was not due to a general lack of biologic activity. Binding studies with 125I-EGF suggest that the EGF receptor on murine lymphocytes is not constitutively expressed, but inducible by the T cell mitogen staphylococcal enterotoxin A. TGF-alpha did not compete with 125I-EGF for the induced receptor. The data suggest that lymphocytes express a novel inducible EGF receptor that differs from that expressed on cells such as 3T3 fibroblasts.
Abdullah
N A
NA
Department of Microbiology and Cell Science, University of Florida, Gainesville 32611.
Torres
B A
BA
Basu
M
M
Johnson
H M
HM
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000502:physiology; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D006133:Growth Substances / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000096:biosynthesis*; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000502:physiology; D015291:Transforming Growth Factors / Q000502:physiology; D014616:Vaccinia virus / Q000502:physiology*
D000276:Adjuvants, Immunologic; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C051087:vaccinia growth factor; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D007371:Interferon-gamma; D066246:ErbB Receptors