Induction of anergic allergen-specific suppressor T cells using tolerogenic dendritic cells derived from children with allergies to house dust mites

J Allergy Clin Immunol. 2010 Mar;125(3):727-36. doi: 10.1016/j.jaci.2009.12.004. Epub 2010 Feb 11.

Abstract

Background: Dendritic cells (DCs) regulate the immune response to allergens in the lung; they induce either effector or regulatory T cells, which promote or suppress, respectively, the development of allergy. IL-10 is a potent immunosuppressive cytokine that induces type 1 regulatory (Tr1) T cells.

Objective: To generate allergen-specific Tr1 cells in vitro from children with allergy.

Methods: Monocyte-derived DCs from children with allergy to house dust mites (HDM) were generated by incubating the cells with IL-10 and pulsing them with Der p 2, a major HDM allergen, or by pulsing them with Der p 2 and incubating them with IL-10 during their last 2 days of differentiation.

Results: Der p 2-specific T-cell proliferation and T(H)2 cytokine production were significantly reduced when T cells from patients with allergy to HDM were activated with autologous Der p 2-pulsed DCs that had been differentiated or incubated with IL-10. T-cell lines generated with Der p 2-pulsed DCs that were differentiated with IL-10 were hyporesponsive to reactivation with Der p 2 and able to suppress Der p 2-specific T(H)2 effector cells.

Conclusion: Dendritic cells differentiated in the presence of IL-10 and pulsed with allergen gave rise to a population of tolerogenic DCs that induced allergen-specific Tr1 cells. This finding represents an important step forward to the prospective clinical application of tolerogenic DCs to modulate allergen-specific T-cell responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • Antigens, Dermatophagoides / immunology*
  • Arthropod Proteins
  • Cell Differentiation / immunology*
  • Cell Proliferation
  • Child
  • Child, Preschool
  • Clonal Anergy / immunology
  • Cysteine Endopeptidases
  • Cytokines / biosynthesis
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Female
  • Humans
  • Hypersensitivity / immunology
  • Immune Tolerance / immunology*
  • Interleukin-10 / immunology
  • Lymphocyte Activation / immunology
  • Male
  • Pyroglyphidae / immunology
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Antigens, Dermatophagoides
  • Arthropod Proteins
  • Cytokines
  • Interleukin-10
  • Cysteine Endopeptidases
  • Dermatophagoides pteronyssinus antigen p 1