Recombinant human IL-4 induces IgE and IgG synthesis by normal and atopic donor mononuclear cells. Similar dose response, time course, requirement for T cells, and effect of pokeweed mitogen.
Unfractionated human blood mononuclear cells (MNC) from normal and atopic donors cultured in enriched Iscove's modified Dulbecco's medium supplemented with 10% FCS responded similarly to stimulation with purified human rIL-4 (rhIL-4) with respect to the concentration required to induce IgE synthesis and the magnitude and kinetics of the IgE response. The IgE response of MNC was IL-4 dose-dependent, increasing linearly with IL-4 concentrations between 0.2 and 2.5 ng/ml and plateauing at concentrations of 5 ng/ml or more. rhIL-4-induced IgE synthesis was first detected at 9 days after stimulation and supernatant IgE concentrations reached a maximum on day 18. rhIL-4 stimulated IgE synthesis by MNC from all donors tested, with peak supernatant IgE concentrations ranging from 3 to 372 ng/ml. The nonatopic group (n = 15) geometric mean peak concentration was 24.0 ng/ml and that of the atopic group (n = 19) was 20.0 ng/ml (p = NS). rhIL-4 also stimulated IgG synthesis by MNC from some (but not all) donors in quantities comparable to those induced by PWM. Maximum supernatant IgG concentrations in responders were found 18 days after stimulation. When PWM was added to the IL-4-stimulated cultures, it completely inhibited rhIL-4-induced IgE and IgG synthesis. rhIL-4 also completely inhibited PWM-induced IgG synthesis. Stimulation of IgE synthesis by rhIL-4 required the presence of T cells. T cell clone supernatants did not support rhIL-4-induced IgE synthesis by B cells. T cells from atopic and nonatopic donors restored rhIL-4-stimulated IgE synthesis by B cells from either source to a similar extent.
Claassen
J L
JL
Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710.
Levine
A D
AD
Buckley
R H
RH
D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D011043:Pokeweed Mitogens / Q000494:pharmacology; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
D007074:Immunoglobulin G; D011043:Pokeweed Mitogens; D011994:Recombinant Proteins; D015847:Interleukin-4; D007073:Immunoglobulin E