Interleukin 4 inhibits the interleukin 2-induced production of its functional antagonist, interferon gamma.
Interferon gamma (IFN gamma) inhibits many effects of interleukin (IL)-4. Its production largely parallels cell proliferation but is regulated independently. As IL-4 inhibits several IL-2-induced effects including proliferation of human peripheral blood mononuclear cells, we investigated its influence on the IL-2-induced IFN gamma production. We found that both absolute IFN gamma production and IFN gamma production per proliferation unit (1000 cpm) in response to IL-2 were inhibited by IL-4. IL-2-induced interferon production was inhibited by IL-4 in both sheep red blood cell rosetting and non-rosetting cells. In bidirectional mixed lymphocyte culture, IL-4 alone enhanced proliferation but suppressed IFN gamma production. As 48% of IFN gamma-producing cells are known to show T cell phenotype, the nearly total inhibition of IFN gamma production is evidence for suppression of T cell response to IL-2. Additionally, we found that the inhibition of IL-2-induced proliferation by IL-4 was significantly more pronounced at low cell densities. Basal proliferation was only inhibited in serum-containing media. These data stress the importance of other lymphokines or accessory cells in the regulation of early lymphocyte activation.
Wagner
F
F
II. Medizinische Klinik und Poliklinik rechts der Isar der Technischen Universität München, F.R.G.
Fischer
N
N
Lersch
C
C
Hart
R
R
Dancygier
H
H
D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000494:pharmacology*; D015847:Interleukin-4; D007378:Interleukins / Q000494:pharmacology*; D011863:Radioimmunoassay; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000378:metabolism
D007376:Interleukin-2; D007378:Interleukins; D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma