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Allergic sensitization can be induced via multiple physiologic routes in an adjuvant- dependent manner  David Dunkin, MD, M. Cecilia Berin, PhD, Lloyd.

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Presentation on theme: "Allergic sensitization can be induced via multiple physiologic routes in an adjuvant- dependent manner  David Dunkin, MD, M. Cecilia Berin, PhD, Lloyd."— Presentation transcript:

1 Allergic sensitization can be induced via multiple physiologic routes in an adjuvant- dependent manner  David Dunkin, MD, M. Cecilia Berin, PhD, Lloyd Mayer, MD  Journal of Allergy and Clinical Immunology  Volume 128, Issue 6, Pages e2 (December 2011) DOI: /j.jaci Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 Antigen-specific serum antibody profile. C3H/HeJ mice were exposed to ALA plus CT by the intragastric (oral; n = 9), sublingual (SL; n = 9), intranasal (IN; n = 5), or cutaneous (skin; n = 5) route for 6 weeks prior to measurement of antigen-specific antibodies in the serum by ELISA. ∗P < .05, ∗∗P < .01, ∗∗∗P < .001 vs none, ¶P < .05 vs oral, IN, SL. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Symptom score and body temperature. C3H/HeJ mice were exposed to ALA ± CT by the intragastric (oral), sublingual (SL), intranasal (IN), or cutaneous (skin) route. Mice were then challenged with progressively increasing oral ALA and 30 minutes after the first dose eliciting symptoms (A) and a decrease in body temperature (B), a symptom score was assigned and body temperature measured. ∗P < .05, ∗∗P < .01, ∗∗∗P < .001 vs nonexposed (none). (n Values are the same as in Fig 1.) Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Effect of CT on skin-draining DCs. A, Effect of CT on migratory DCs and their subsets in the draining lymph node; n = 6. B, Effect of CT on migration of FITC-dextran-positive DCs to the draining lymph nodes; n = 3, experiments of 3 Balb/c mice/group. C, Median fluorescent intensity (MFI) of MHC class II of FITC-dextran-positive DCs; n = 3, experiments of 3 Balb/c mice/group. D, Representative flow cytometry plot showing the phenotype of FITC-dextran-positive DCs (lower panel) compared with the total migratory DC population (upper panel). n = 3, ∗P < .05, ∗∗P < .01. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 Effect of CT on the antigen-specific T-cell response. A representative histogram (A) and quantification (B) of proliferation of DO11.10 T cells in the SLN after exposure to PBS, OVA, or OVA + CT. n = 5 (C) Cytokine secretion from transferred OVA-specific T cells after in vivo exposure to PBS, OVA, or OVA + CT after restimulation with OVA peptide and subsequent stimulation with anti-CD3/CD28. n = 3 experiments of 3 Balb/c mice/group. ∗P < .05, ∗∗P < .01, ∗∗∗P < .001. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 Effect of in vivo treatment with CT on the immunogenicity of DCs. DCs were purified from the inguinal lymph node of Balb/c mice treated topically with PBS, OVA, or OVA + CT and cocultured with DO11.10 cells. Levels of secreted cytokines were measured by ELISA after restimulation with OVA peptide and subsequent stimulation with anti-CD3/CD28. n = 2 experiments of 3 mice/group, ∗∗P < .01, ∗∗∗P < .001. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig E1 In vitro splenocyte stimulation cytokine profile. Mice were exposed to ALA plus CT by the intragastric (oral), sublingual (SL), intranasal (IN), or cutaneous (skin) route for 6 weeks, challenged, and sacrificed prior to an in vitro stimulation of splenocytes with ALA. Cytokines were determined by ELISA. Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 Fig E2 Effect of CT on skin-draining DCs in C3H/HeJ mice. A, Effect of CT on migration of FITC-dextran-positive DCs to the draining lymph nodes; n = 2 experiments of 3 mice/group. B, Representative flow cytometry plot showing the phenotype of FITC-dextran-positive DCs (lower panel) compared with the total migratory DC population (upper panel). Journal of Allergy and Clinical Immunology  , e2DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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