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Prophylactic and therapeutic vaccination with carrier-bound Bet v 1 peptides lacking allergen-specific T cell epitopes reduces Bet v 1-specific T cell responses via blocking antibodies in a murine model for birch pollen allergy.

Linhart B, Narayanan M, Focke-Tejkl M, Wrba F, Vrtala S, Valenta R - Clin. Exp. Allergy (2014)

Bottom Line: The effects of peptide-specific and allergen-specific antibodies on T cell responses and allergic lung inflammation were studied using specific antibodies.Prophylactic and therapeutic vaccination of mice with the peptide vaccine induced Bet v 1-specific antibodies which suppressed Bet v 1-specific T cell responses and allergic lung inflammation.Vaccination with carrier-bound allergen-derived peptides lacking allergen-specific T cell epitopes induces allergen-specific IgG antibodies which suppress allergen-specific T cell responses and allergic lung inflammation.

View Article: PubMed Central - PubMed

Affiliation: Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.

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Inhibition of Bet v 1-specific T cell proliferation by Bet v 1-specific antibodies. (a) Splenocytes from four Bet v 1-sensitized mice were stimulated in the presence of normal mouse serum, serum from the S+/T+ group, or serum from the P+/S+ group from day 120 or (b) in the presence of normal mouse serum or different concentrations of mouse or rabbit anti-Bet v 1 peptide antisera. (c) Experiment performed as in (a, b) with cultured splenocytes without rabbit serum or with rabbit antisera specific for Phl p 1, Bet v 1, Bet v 1 fragments, Bet v 1 trimer, or Bet v 1 peptides. Stimulation indices ± SD are shown for triplicate cultures from 4 individual mice (y-axes).
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fig07: Inhibition of Bet v 1-specific T cell proliferation by Bet v 1-specific antibodies. (a) Splenocytes from four Bet v 1-sensitized mice were stimulated in the presence of normal mouse serum, serum from the S+/T+ group, or serum from the P+/S+ group from day 120 or (b) in the presence of normal mouse serum or different concentrations of mouse or rabbit anti-Bet v 1 peptide antisera. (c) Experiment performed as in (a, b) with cultured splenocytes without rabbit serum or with rabbit antisera specific for Phl p 1, Bet v 1, Bet v 1 fragments, Bet v 1 trimer, or Bet v 1 peptides. Stimulation indices ± SD are shown for triplicate cultures from 4 individual mice (y-axes).

Mentions: Results obtained showed that serum from peptide-vaccinated mice suppressed Bet v 1-specific proliferation of splenocytes from Bet v 1-sensitized mice (Fig.7a). Moreover, we could show that only sera generated by vaccination of mice and rabbits with the Bet v 1-derived peptides, Bet v 1, recombinant Bet v 1 derivatives but not other control antigens had a suppressive effect on allergen-specific proliferation, suggesting that the proliferation of Bet v 1-specific T cells was indeed suppressed by Bet v 1-specific antibodies (Figs7b and c). Furthermore, we extended the study comparing the effect of the peptide vaccine to prophylactic and therapeutic vaccination with wild-type Bet v 1, with a mixture of two Bet v 1 fragments or with a Bet v 1 trimer, which have already been used for vaccination in patients in clinical trials 16,28. Using these molecules for prophylactic and therapeutic vaccination, we could again observe a suppressive effect on splenocyte proliferation (Figure S5).


Prophylactic and therapeutic vaccination with carrier-bound Bet v 1 peptides lacking allergen-specific T cell epitopes reduces Bet v 1-specific T cell responses via blocking antibodies in a murine model for birch pollen allergy.

Linhart B, Narayanan M, Focke-Tejkl M, Wrba F, Vrtala S, Valenta R - Clin. Exp. Allergy (2014)

Inhibition of Bet v 1-specific T cell proliferation by Bet v 1-specific antibodies. (a) Splenocytes from four Bet v 1-sensitized mice were stimulated in the presence of normal mouse serum, serum from the S+/T+ group, or serum from the P+/S+ group from day 120 or (b) in the presence of normal mouse serum or different concentrations of mouse or rabbit anti-Bet v 1 peptide antisera. (c) Experiment performed as in (a, b) with cultured splenocytes without rabbit serum or with rabbit antisera specific for Phl p 1, Bet v 1, Bet v 1 fragments, Bet v 1 trimer, or Bet v 1 peptides. Stimulation indices ± SD are shown for triplicate cultures from 4 individual mice (y-axes).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215111&req=5

fig07: Inhibition of Bet v 1-specific T cell proliferation by Bet v 1-specific antibodies. (a) Splenocytes from four Bet v 1-sensitized mice were stimulated in the presence of normal mouse serum, serum from the S+/T+ group, or serum from the P+/S+ group from day 120 or (b) in the presence of normal mouse serum or different concentrations of mouse or rabbit anti-Bet v 1 peptide antisera. (c) Experiment performed as in (a, b) with cultured splenocytes without rabbit serum or with rabbit antisera specific for Phl p 1, Bet v 1, Bet v 1 fragments, Bet v 1 trimer, or Bet v 1 peptides. Stimulation indices ± SD are shown for triplicate cultures from 4 individual mice (y-axes).
Mentions: Results obtained showed that serum from peptide-vaccinated mice suppressed Bet v 1-specific proliferation of splenocytes from Bet v 1-sensitized mice (Fig.7a). Moreover, we could show that only sera generated by vaccination of mice and rabbits with the Bet v 1-derived peptides, Bet v 1, recombinant Bet v 1 derivatives but not other control antigens had a suppressive effect on allergen-specific proliferation, suggesting that the proliferation of Bet v 1-specific T cells was indeed suppressed by Bet v 1-specific antibodies (Figs7b and c). Furthermore, we extended the study comparing the effect of the peptide vaccine to prophylactic and therapeutic vaccination with wild-type Bet v 1, with a mixture of two Bet v 1 fragments or with a Bet v 1 trimer, which have already been used for vaccination in patients in clinical trials 16,28. Using these molecules for prophylactic and therapeutic vaccination, we could again observe a suppressive effect on splenocyte proliferation (Figure S5).

Bottom Line: The effects of peptide-specific and allergen-specific antibodies on T cell responses and allergic lung inflammation were studied using specific antibodies.Prophylactic and therapeutic vaccination of mice with the peptide vaccine induced Bet v 1-specific antibodies which suppressed Bet v 1-specific T cell responses and allergic lung inflammation.Vaccination with carrier-bound allergen-derived peptides lacking allergen-specific T cell epitopes induces allergen-specific IgG antibodies which suppress allergen-specific T cell responses and allergic lung inflammation.

View Article: PubMed Central - PubMed

Affiliation: Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.

Show MeSH