The relative contribution of IL-4 and IL-13 to human IgE synthesis induced by activated CD4+ or CD8+ T cells Juha Punnonen, MD, PhD, Hans Yssel, PhD,

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Presentation transcript:

The relative contribution of IL-4 and IL-13 to human IgE synthesis induced by activated CD4+ or CD8+ T cells Juha Punnonen, MD, PhD, Hans Yssel, PhD, Jan de Vries, PhD Journal of Allergy and Clinical Immunology Volume 100, Issue 6, Pages 792-801 (December 1997) DOI: 10.1016/S0091-6749(97)70276-8 Copyright © 1997 Mosby, Inc. Terms and Conditions

FIG. 1 IL-13 additively enhances IgE synthesis induced by suboptimal concentrations of IL-4. Human PBMC were cultured in the presence of IL-4 (0, 0.5, or 50 ng/ml) and increasing concentrations of IL-13 were added to cultures. IgE levels in culture supernatants were measured by ELISA after culture for 12 days. Data represent mean ± SEM IgE levels of quadruplicate cultures in a representative of four experiments. Journal of Allergy and Clinical Immunology 1997 100, 792-801DOI: (10.1016/S0091-6749(97)70276-8) Copyright © 1997 Mosby, Inc. Terms and Conditions

FIG. 2 Effects of neutralizing mAbs specific for IL-4 and IL-13 on IgE and IgG4 (A) or IgM, total IgG, and IgA (B) synthesis induced by supernatants of activated CD4+ T cell clones, and effects of these mAbs on IgE synthesis induced by recombinant IL-4 or IL-13 (C). Supernatants (25% of final volume) of CD4+ T cells activated by immobilized anti-CD3 and anti-CD28 mAbs (A and B), or recombinant IL-4 (100 ng/ml) or IL-13 (100 ng/ml) (C) were added to cultures of purified B cells stimulated with anti-CD40 mAbs (10 μg/ml) in the presence or absence of neutralizing anti–IL-4 or anti–IL-13 mAbs (10 μg/ml each) as indicated in the figure. Ig synthesis was studied after culture for 12 to 14 days by specific ELISAs. In A and B, 17 supernatants were studied with the use of splenic B cells from four different donors in a total of 25 experiments, and levels of Ig produced in the presence of neutralizing mAbs are expressed as percentages (mean ± SEM) of those produced in the absence of the mAbs. Mean levels of IgE, IgG4, IgM, total IgG, and IgA detected in these experiments were 230, 569, 1852, 2152, and 3566 ng/ml, respectively. In C, data represent mean (±SEM) IgE levels of quadruplicate cultures in a representative of four experiments. Journal of Allergy and Clinical Immunology 1997 100, 792-801DOI: (10.1016/S0091-6749(97)70276-8) Copyright © 1997 Mosby, Inc. Terms and Conditions

FIG. 3 Correlation of levels of IL-4 (A), IL-13 (B), and IFN-γ (C) in CD4+ T cell supernatants with the amount of IgE induced by the supernatants, and production levels of IL-4, IL-13, and IFN-γ by activated CD4+ T cells (D, E and F,respectively). Cytokine levels were studied by specific ELISAs in 23 supernatants derived from 15 different CD4+ T cell clones activated with immobilized anti-CD3 and anti-CD28 mAbs and the capacities of the supernatants to induce IgE were studied. Purified B cells were cultured in the presence of anti-CD40 mAbs (10 μg/ml) and T cell supernatants (25% of final volume), and levels of IgE produced were studied after culture for 12 to 14 days. Journal of Allergy and Clinical Immunology 1997 100, 792-801DOI: (10.1016/S0091-6749(97)70276-8) Copyright © 1997 Mosby, Inc. Terms and Conditions

FIG. 4 Effects of neutralizing anti–IL-4 and anti–IL-13 mAbs on IgE synthesis induced in response to supernatants of CD4+ T cell lines derived from skin of patients with atopic dermatitis. Skin-derived T cell lines were generated after allergen challenge as described in Methods section and activated with immobilized anti-CD3 and anti-CD28 mAbs for 48 hours before harvesting the supernatants. Purified B cells (105/well) were cultured in the presence of T cell supernatant (25% of final volume), anti-CD40 mAbs (10 μg/ml), and anti–IL-4 and/or anti–IL-13 mAbs (10 μg/ml). IgE levels in culture supernatants were measured after culture for 12 days. IL-4, IL-13, and IFN-γ levels (ng/ml) detected in each supernatant are indicated in the figure. Journal of Allergy and Clinical Immunology 1997 100, 792-801DOI: (10.1016/S0091-6749(97)70276-8) Copyright © 1997 Mosby, Inc. Terms and Conditions

FIG. 5 Effects of neutralizing anti–IL-4 and anti–IL-13 mAbs on IgE synthesis induced in response to supernatants of TH1-like T cell clones. Supernatants (25% of final volume) derived from T cell clones generated from CD4+ naive cord blood T cells in the presence of IL-12 (A and B) or adult TH1 clones (C and D) were cultured in the presence of purified B cells (105/well), anti-CD40 mAbs, and anti–IL-4 and/or anti–IL-13 mAbs (10 μg/ml). T cell clones were activated with immobilized mAbs anti-CD3 and anti-CD28 for 48 hours before harvesting the supernatants. IgE levels in the culture supernatants were measured after culture for 12 days. IL-4, IL-13, and IFN-γ levels (ng/ml) detected in each supernatant are indicated in the figure. Journal of Allergy and Clinical Immunology 1997 100, 792-801DOI: (10.1016/S0091-6749(97)70276-8) Copyright © 1997 Mosby, Inc. Terms and Conditions

FIG. 6 Effects of neutralizing anti–IL-4 and anti–IL-13 mAbs on IgE synthesis induced by supernatants of CD8+ T cell clones. CD8+ T cell clones were activated with mAbs anti-CD3 and anti-CD28 for 48 hours before harvesting the supernatants. Purified B cells (105/well) were cultured in the presence of T cell supernatants (25% of final volume), anti-CD40 mAbs, anti-IFN-γ, anti–IL-4, and/or anti–IL-13 mAbs (10 μg/ml each). IgE levels in the culture supernatants were measured after culture for 12 days. Journal of Allergy and Clinical Immunology 1997 100, 792-801DOI: (10.1016/S0091-6749(97)70276-8) Copyright © 1997 Mosby, Inc. Terms and Conditions