Functional Analysis of Birch Pollen Allergen Bet v 1-Specific Regulatory T Cells

Abstract

Allergen-specific immunotherapy using peptides is an efficient treatment for allergic diseases. Recent studies suggest that the induction of CD4+ regulatory T (Treg) cells might be associated with the suppression of allergic responses in patients after allergen-specific immunotherapy. Our aim was to identify MHC class II promiscuous T cell epitopes for the birch pollen allergen Bet v 1 capable of stimulating Treg cells with the purpose of inhibiting allergic responses. Ag-reactive CD4+ T cell clones were generated from patients with birch pollen allergy and healthy volunteers by in vitro vaccination of PBMC using Bet v 1 synthetic peptides. Several CD4+ T cell clones were induced by using 2 synthetic peptides (Bet v 1141–156 and Bet v 151–68). Peptide-reactive CD4+ T cells recognized recombinant Bet v 1 protein, indicating that these peptides are produced by the MHC class II Ag processing pathway. Peptide Bet v 1141–156 appears to be a highly MHC promiscuous epitope since T cell responses restricted by numerous MHC class II molecules (DR4, DR9, DR11, DR15, and DR53) were observed. Two of these clones functioned as typical Treg cells (expressed CD25, GITR, and Foxp3 and suppressed the proliferation and IL-2 secretion of other CD4+ T cells). Notably, the suppressive activity of these Treg cells required cell-cell contact and was not mediated through soluble IL-10 or TGF-β. The identified promiscuous MHC class II epitope capable of inducing suppressive Treg responses may have important implication for the development of peptide-based Ag-specific immunotherapy to birch pollen allergy.

Novel Vaccination for Allergy through Gene Silencing of CD40 Using Small Interfering RNA

“…It has been reported that Treg cells inhibits T cell response against allergic Ags and production of Th2 cytokines (43)(44)(45)(46). Because silencing of CD40 was also associated with acquisition of a tolerogenic or Treg-generating DC subset, we sought to determine whether allergic responses might benefit from such an approach.…”

Neuropeptide signaling through neurokinin-1 and neurokinin-2 receptors augments antigen presentation by human dendritic cells

“…E4 in the Online Repository), as described previously. 5,6 T-cell proliferation and cytokine production was evaluated after stimulation with antigen-loaded MoDCs. Blocking NK2R-mediated signaling suppressed the induction of antigen-specific CD4 + T cells (Fig.…”

Immune Regulation by CD4+CD25+ Regulatory T Cells in Patients with Japanese Cedar Pollinosis

“…Depletion of CD4+CD25+ Treg cells resulted in the reduction of IL-10 production upon stimulation with Cry j 1; therefore, we investigated the presence of Cry j 1-specific IL-10-producing CD4+ CD25+ Treg cells using IL-10 ELISPOT assays. In general, the suppressive effect of CD4+CD25+ Treg cells is known to be dose dependent, cell-contact dependent, cytokine independent and antigen nonspecific; however, several reports have demonstrated that allergen-specific IL-10-producing CD4+CD25+ T cells exist in peripheral blood in allergic patients [12,13]. Furthermore, such T cells have also been shown to be induced and increased in patients undergoing immunotherapy [23,24].…”

“…Maggi et al [12] have identified circulating Der p 1-specific CD4+CD25+FOXP3+ Treg cells from nonatopic and atopic individuals. Nagato et al [13] have also demonstrated that Bet v 1-specific CD4+CD25+ FOXP3+ Treg cells are obtained from patients with birch pollen nasal allergy. These findings suggest overlapping allergen-specific subsets within CD4+CD25+ cells and antigen-induced IL-10-secreting Treg cells.…”