Immunomodulatory effects of aqueous birch pollen extracts and phytoprostanes on primary immune responses in vivo Jan Gutermuth, MD, Mayte Bewersdorff,

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Presentation transcript:

Immunomodulatory effects of aqueous birch pollen extracts and phytoprostanes on primary immune responses in vivo Jan Gutermuth, MD, Mayte Bewersdorff, MSc, Claudia Traidl-Hoffmann, MD, Johannes Ring, MD, PhD, Martin J. Mueller, PhD, Heidrun Behrendt, MD, Thilo Jakob, MD Journal of Allergy and Clinical Immunology Volume 120, Issue 2, Pages 293-299 (August 2007) DOI: 10.1016/j.jaci.2007.03.017 Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Bet-APEs and PPE1 inhibit murine DC IL-12 production. DCs were stimulated with 100 ng/mL LPS in the presence of increasing concentrations of Bet-APEs, PPE1, or PPF1. After 20 hours, IL-12p70 concentrations were determined in culture supernatants by means of ELISA. Data are presented as percentages of LPS-induced IL-12p70 production (means ± SEMs) to equalize donor-specific variability (IL12p70: 100% = 1599 ± 437 pg/mL; Bet-APE: n = 7; PPE1: n = 5; PPF1: n = 3). Journal of Allergy and Clinical Immunology 2007 120, 293-299DOI: (10.1016/j.jaci.2007.03.017) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 TH2-polarizing effects of Bet-APEs on primary immune responses in vitro. The intracellular cytokine accumulation in OVA-specific DO11.10 T cells 6 days after antigen stimulation in a chimeric DO11.10/BALB/c splenocyte culture is shown. The percentage of IL-4/IFN-γ–producing OVA-specific T cells (gated on KJ1-26+ cells) after antigen stimulation in the absence (OVA) or presence of Bet-APEs (OVA, Bet-APEs) is also shown. TH1 and TH2 controls were stimulated with OVA, IL-12, and anti-IL-4 or OVA, IL-4, and anti-IL-12, respectively. A, One representative experiment of 5. B, Means ± SEMs of 5 experiments. Journal of Allergy and Clinical Immunology 2007 120, 293-299DOI: (10.1016/j.jaci.2007.03.017) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Intranasal Bet-APEs induce a TH2 shift in draining cervical lymph nodes, whereas exposure to phytoprostanes inhibit TH1 and TH2 induction. DO11.10/BALB/c chimeric mice were exposed intranasally to 2 mM OVA (20 μL) with or without Bet-APEs (6 μg/20 μL) or PPE1 or PPF1 at indicated concentrations. After 48 hours, nose-draining cervical lymph nodes were excised, single-cell suspensions were restimulated ex vivo, and supernatants were analyzed after 3 days for IL-4, IL-5, IL-13, and IFN-γ by means of ELISA (A) or antigen-specific T cells were analyzed after 6 days for intracellular cytokine production at the single-cell level by means of flow cytometry (B). ELISA data are presented as percentages of OVA-induced cytokine production (mean ± SEM: IFN-γ 100% = 626 ± 111 pg/mL; IL-4: 100% = 14 ± 8 pg/mL; IL-5: 100% = 12 ± 4 pg/mL; IL-13: 100% = 149 ± 39 pg/mL). Fig 3, A and B: 5 independent experiments with 3 animals per group. Journal of Allergy and Clinical Immunology 2007 120, 293-299DOI: (10.1016/j.jaci.2007.03.017) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Intranasal exposure to phytoprostanes but not to Bet-APEs inhibits antigen-induced T-cell proliferation in draining lymph nodes in vivo. In vivo division kinetics of carboxyfluorescein diacetate succinimidyl ester–labeled OVA-specific T cells in nose-draining cervical lymph nodes of DO11.10/BALB/c chimeras 48 hours after intranasal exposure to PBS (solid line) or OVA (2 mM, 20 μL) in the presence or absence of Bet-APEs (6 μg/20 μL) or phytoprostanes (10−6 M; filled curve) are shown. Journal of Allergy and Clinical Immunology 2007 120, 293-299DOI: (10.1016/j.jaci.2007.03.017) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions