Augmentation of regulatory T cells in allergic individuals by recombinant Der f 2 peptide with fungal immunomodulatory peptide fve

Abstract

Background: The suppressive function of regulatory T (Treg) cells is compromised in allergic individuals, and the augmentation of Treg cells has been demonstrated after successful allergen immunotherapy. Objective: To evaluate the effect of Dermatophagoides farinae fragments (Der f 2 N-peptides) that do not bind specific IgE in conjunction with the fungal immunomodulatory peptide fve (FIP-fve) on Treg cells derived from individuals with allergic rhinitis. Methods: CD4(+)CD25(+) T cells were isolated from peripheral blood mononuclear cells of I I patients with allergic rhinitis and 7 nonallergic individuals using immunomagnetic beads. Cells were cultured with medium, Der f 2, FIP-fve, FIP-fve plus Der f 2, and FIP-fve plus Der f 2 N-peptides for 6 days in the presence of antigen-presenting cells. The percentages and function of Foxp3(+)CD4(+)CD25(+) Treg cells, interleukin (IL) 10(+), and transforming growth factor beta (TGF-beta)(+) Treg cells were measured. Results: The percentage of Foxp3(+) Treg cells in CD4(+)CD25(+) T cells was significantly increased in D farinae allergic patients by Der f 2 N-peptides in conjunction with FIP-fve. Both IL-10(+) and TGF-beta(+) Treg cells were significantly increased in the presence of Der f 2 N-peptides and FIP-fve compared with other groups. The function of Treg cells induced by Der f 2 N-peptides and FIP-fve could be demonstrated by the inhibition of bromodeoxyuridine uptake by peripheral blood mononuclear cells. Conclusion: The percentage of IL-10(+) and TGF-beta(+) cells in Foxp3(+)CD4(+)CD25(+) T cells can be up-regulated by Der f 2 N-peptides in conjunction with FIP-fve only in Dfarinae allergic individuals. These results indicate that non-IgE-mediated fragments of allergen in conjunction with FIP-fve might have therapeutic effects on Treg cells derived from allergic individuals.