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Suppression of antigen-specific T- and B-cell responses by intranasal or oral administration of recombinant Bet v 1, the major birch pollen allergen,

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Presentation on theme: "Suppression of antigen-specific T- and B-cell responses by intranasal or oral administration of recombinant Bet v 1, the major birch pollen allergen,"— Presentation transcript:

1 Suppression of antigen-specific T- and B-cell responses by intranasal or oral administration of recombinant Bet v 1, the major birch pollen allergen, in a murine model of type I allergy  Ursula Wiedermann, MD, PhDa, Beatrice Jahn-Schmid, PhDa,b, Barbara Bohle, MSca, Andreas Repa a, Harald Renz, MDc, Dietrich Kraft, MDa, Christof Ebner, MDa  Journal of Allergy and Clinical Immunology  Volume 103, Issue 6, Pages (June 1999) DOI: /S (99) Copyright © 1999 Mosby, Inc. Terms and Conditions

2 Fig. 1 Serum IgG1, IgG2a and IgE antibody levels against BP and recombinant Bet v 1 (rBet) . Open bars indicate mean optical density (OD) of 6 mice immunized intraperitoneally with rBet v 1/Al(OH)3 and subsequently aerosolized with BP extract (group 3). Hatched bars indicate mean OD of 6 mice orally treated with rBet v 1 before sensitization (group 2), and filled bars indicate mean OD of 6 mice intranasally administered rBet v 1 before sensitization (group 1). Error bars indicate SEMs. *P < .05, **P < .01 as determined by the Mann-Whitney U test. Journal of Allergy and Clinical Immunology  , DOI: ( /S (99) ) Copyright © 1999 Mosby, Inc. Terms and Conditions

3 Fig. 2 Total serum IgG and IgE immunoglobulin levels. Open bars indicate mean optical density (OD) of 6 mice immunized intraperitoneally with rBet v 1/Al(OH)3 and subsequently aerosolized with BP extract (group 3). Hatched bars indicate mean OD of 6 mice orally treated with rBet v 1 before sensitization (group 2), and filled bars show mean OD of 6 mice intranasally administered rBet v 1 before sensitization (group 1). Error bars indicate SEMs. n.s., Nonsignificant as determined by the Mann-Whitney U test. Journal of Allergy and Clinical Immunology  , DOI: ( /S (99) ) Copyright © 1999 Mosby, Inc. Terms and Conditions

4 Fig. 3 Representative skin sections of type I skin tests of mice sensitized with rBet v1/Al(OH)3 intraperitoneally (i.p.) before BP aerosol exposure (group 3), mice treated 3 times orally with 100 μg rBet v1 (group 2), and mice treated 3 times intranasally (i.n.) with 10 μg rBet v 1 before sensitization (group 1). Skin reactions to BP (2.5 μg/mL) and rBet v 1 (2.5 μg/mL), histamine-releasing compound 48/80 (20 μg/mL), and PBS were measured at the inside of the abdominal skin 20 minutes after intradermal injection. Journal of Allergy and Clinical Immunology  , DOI: ( /S (99) ) Copyright © 1999 Mosby, Inc. Terms and Conditions

5 Fig. 4 Cytokine production in spleen cell cultures. IL-4 and IL-5 levels were measured after 24 hours, and IFN-γ and IL-10 levels were measured 48 hours after stimulation with BP. Open bars indicate mean values (pg/mL) of 6 mice immunized intraperitoneally with rBet v 1/Al(OH)3 and subsequently aerosolized with BP extract (group 3). Hatched bars indicate mean values (pg/mL) of 6 mice orally treated with rBet v 1 before sensitization (group 2), and black bars show mean values (pg/mL) of 6 mice intranasally administered rBet v1 before sensitization (group 1). Error bars indicate SEMs. *P < .05, **P < .001 as determined by the Mann-Whitney U test. Journal of Allergy and Clinical Immunology  , DOI: ( /S (99) ) Copyright © 1999 Mosby, Inc. Terms and Conditions

6 Fig. 5 TGF-β mRNA expression in spleen cells of 5 sensitized (group 3) and 5 nasally tolerized mice (group 1). Bars indicate ratio of β-actin/TGF-β and are expressed as mean values of 4 individual PCR experiments. Error bars indicate SEMs. *P < .05 as determined by the Mann-Whitney U test. Journal of Allergy and Clinical Immunology  , DOI: ( /S (99) ) Copyright © 1999 Mosby, Inc. Terms and Conditions

7 Fig. 6 Proposed mechanism of mucosal tolerance induction in a TH2 model. Mucosal (oral or nasal) administration of low doses of soluble antigen/allergen may lead to induction of a third subset of T-helper cells, termed TH3 (or Tr) cells, in the mucosa-associated lymphoid tissues. These regulatory T cells, which may also migrate to the systemic sites, produce inhibitory cytokines, such as TGF-β.9,23 The preferential production of this cytokine may then lead to an active suppression of antigen-specific TH2 and TH1 cells and consequently no antibody production to the respective antigen/allergen at the effector sites of the immune system. PP, Peyer’s patch; LP, lamina propria; APC, antigen-presenting cells. Journal of Allergy and Clinical Immunology  , DOI: ( /S (99) ) Copyright © 1999 Mosby, Inc. Terms and Conditions

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