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Inhibition of human allergic T-cell responses by IL-10–treated dendritic cells: Differences from hydrocortisone-treated dendritic cells  Iris Bellinghausen,

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Presentation on theme: "Inhibition of human allergic T-cell responses by IL-10–treated dendritic cells: Differences from hydrocortisone-treated dendritic cells  Iris Bellinghausen,"— Presentation transcript:

1 Inhibition of human allergic T-cell responses by IL-10–treated dendritic cells: Differences from hydrocortisone-treated dendritic cells  Iris Bellinghausen, PhD, Udo Brand, PhD, Kerstin Steinbrink, MD, Alexander H. Enk, MD, Jürgen Knop, MD, Joachim Saloga, MD  Journal of Allergy and Clinical Immunology  Volume 108, Issue 2, Pages (August 2001) DOI: /mai Copyright © 2001 Mosby, Inc. Terms and Conditions

2 Fig. 1 Modulation of surface marker expression of allergen-pulsed DCs by IL-10 and HC. DCs were matured without (control ) or with the addition of IL-10 or HC on day 7 of culture. After 48 hours, cells were double-stained for HLA-DR and additional marker, as indicated. The figure shows 1 representative example, including the mean fluorescence intensity and the percentage of positive cells (for CD83), of 15 separate experiments. Journal of Allergy and Clinical Immunology  , DOI: ( /mai ) Copyright © 2001 Mosby, Inc. Terms and Conditions

3 Fig. 2 Inhibition of cytokine production of allergen-pulsed mature DCs by treatment with IL-10 and HC. DCs were matured without (control ) or with the addition of IL-10 or HC on day 7 of culture. Supernatants were harvested 24 hours later for assessment of IL-12p40 and IL-12p70 (n = 11) production and after 48 hours for analysis of IL-6 (n = 11) and IL-10 (n = 9) production by ELISA. The results represent the means ± SDs. Asterisks indicate statistically significant differences (P ≤ .05) between untreated and IL-10– or HC-treated DCs. n.s., Not shown. Journal of Allergy and Clinical Immunology  , DOI: ( /mai ) Copyright © 2001 Mosby, Inc. Terms and Conditions

4 Fig. 3 Inhibition of the T cell–stimulatory capacity of allergen-pulsed DCs by IL-10 and HC. 1 × 105 CD45RA+ or CD45R0+ CD4+ T cells were stimulated with titrated numbers of autologous allergen-pulsed DCs, either pretreated with IL-10 or HC or else untreated. After 5 days, the cells were pulsed with 1 μCi of [3H]TdR for 6 hours before harvesting. The data represent the means ± SDs from 8 independent experiments. Asterisks indicate statistically significant differences (P ≤ .05) between untreated and IL-10– or HC-treated DCs. Journal of Allergy and Clinical Immunology  , DOI: ( /mai ) Copyright © 2001 Mosby, Inc. Terms and Conditions

5 Fig. 4 IL-10– or HC-treated DCs differentially modulate cytokine production of naive and memory T helper cells from atopic donors. 5 × 105 CD45RA+ or CD45R0+ CD4+ T cells were stimulated with 5 × 104 autologous allergen-pulsed DCs, either pretreated with IL-10 or HC or else untreated. After 1 week of culture, T cells were restimulated with 5 × 104 newly generated DCs or with IL-10– or HC-treated DCs of the same donor. Supernatants were collected 24 hours later and analyzed for IL-4, IL-5, and IFN-γ content by ELISA. Shown are the means ± SDs from 19 (for IL-10–treated DCs) and 16 (for HC-treated DCs) independent experiments. Asterisks indicate statistically significant differences (P ≤ .05) between untreated and IL-10– or HC-treated DCs. Journal of Allergy and Clinical Immunology  , DOI: ( /mai ) Copyright © 2001 Mosby, Inc. Terms and Conditions

6 Fig. 5 Long-lasting and stable effect of IL-10– or HC-pretreatment of DCs on cytokine production by T cells. 5 × 105 CD45RA+ or CD45R0+ CD4+ T cells were primarily stimulated with 5 × 104 autologous allergen-pulsed DCs, either pretreated with IL-10 or HC or else untreated. After 1 week of culture, T cells were restimulated with 5 × 104 newly generated, fully mature, allergen-pulsed DCs of the same donor. Supernatants were collected 24 hours later and analyzed for IL-4, IL-5, and IFN-γ content by ELISA. Shown are the means ± SDs from 26 (for IL-10–treated DCs) and 24 (for HC-treated DCs) independent experiments. Asterisks indicate statistically significant differences (P ≤ .05) between untreated and IL-10– or HC-treated DCs. Journal of Allergy and Clinical Immunology  , DOI: ( /mai ) Copyright © 2001 Mosby, Inc. Terms and Conditions

7 Fig. 6 IL-2 restores the cytokine response to cells previously inhibited by coculture with IL-10– or HC-treated DCs. 5 × 105 CD45RA+ CD4+ T cells were primarily stimulated with 5 × 104 autologous allergen-pulsed DCs, either pretreated with IL-10 or HC or else untreated. After 1 week of culture, T cells were restimulated with 5 × 104 newly generated, mature, allergen-pulsed DCs of the same donor without or with the addition of 100 U/mL IL-2. Supernatants were collected 24 hours later and analyzed for IL-4, IL-5, and IFN-γ content by ELISA. Shown are the means ± SDs from 8 independent experiments. Journal of Allergy and Clinical Immunology  , DOI: ( /mai ) Copyright © 2001 Mosby, Inc. Terms and Conditions

8 Fig. 7 IL-10– and HC-pretreated DCs differentially modulate allergen-specific T-cell responses. Whereas pretreatment of allergen-pulsed DCs with IL-10 induces functional hyporesponsiveness of allergen-specific TH1 and TH2 cells, HC-pretreated DCs inhibit TH1 but not TH2 cells. Journal of Allergy and Clinical Immunology  , DOI: ( /mai ) Copyright © 2001 Mosby, Inc. Terms and Conditions

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