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

Ann Allergy Asthma Immunol. 2009 Mar;102(3):216-22. doi: 10.1016/S1081-1206(10)60084-1.

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 11 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 D farinae 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Dermatophagoides / genetics
  • Antigens, Dermatophagoides / immunology*
  • Arthropod Proteins
  • Case-Control Studies
  • Cell Proliferation
  • Cytokines / metabolism
  • Fungal Proteins / genetics
  • Fungal Proteins / immunology*
  • Humans
  • Interleukin-10 / metabolism
  • Lectins / genetics
  • Lectins / immunology*
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Lymphocyte Activation / immunology
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology
  • Recombinant Proteins / immunology*
  • Rhinitis, Allergic, Perennial / immunology*
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Transforming Growth Factor beta / metabolism

Substances

  • Antigens, Dermatophagoides
  • Arthropod Proteins
  • Cytokines
  • Dermatophagoides farinae antigen f 2
  • Fungal Proteins
  • IL10 protein, human
  • Lectins
  • Peptide Fragments
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • Interleukin-10