Recombinant Culicoides obsoletus complex allergens stimulate antigen-specific T cells of insect bite hypersensitive Shetland ponies in vitro

Vet Dermatol. 2015 Dec;26(6):467-75, e108-9. doi: 10.1111/vde.12251. Epub 2015 Sep 8.

Abstract

Background: Ponies may suffer from Insect bite hypersensitivity (IBH), an allergic IgE-mediated pruritic skin disorder, induced by allergens from biting midges of the Culicoides spp.

Hypothesis/objectives: To determine whether recombinant Culicoides obsoletus allergens are able to activate T cells of ponies exposed to C. obsoletus and whether these allergen-specific responses differ between IBH-affected and healthy ponies.

Animals: Ten IBH-affected Shetland ponies and 10 age-matched healthy controls taken from the same stables, to ensure similar exposure to midges.

Method: Peripheral blood mononuclear cells (PBMC) were cultured with two different pools of recombinant C. obsoletus complex allergens to expand the allergen-specific T cells. These PBMC cultures were subsequently co-cultured with mature dendritic cells (DCs) loaded with the same antigens. Induction of Th1, Th2 and regulatory T (Treg) cells in these DC/PBMC co-cultures was assessed by analysis of IFN-γ, IL-4, IL-10 and FoxP3 expression levels using quantitative RT-PCR and phenotyping by flow cytometry.

Results: Recombinant C. obsoletus allergens increased IFN-γ mRNA expression levels, percentages of IFN-γ expressing (Th1) cells and CD25(high) FoxP3(+) IL-10(+) Tregs compared to unstimulated DC/PBMC co-cultures. Stimulation of IL-4 expressing Th2 cells by the recombinant allergens was far less pronounced. The DC/PBMC co-cultures did not reveal significant differences between healthy and IBH-affected ponies for any of the analysed parameters, except for higher IL-4 mRNA levels in IBH affected ponies after stimulation with one of the two allergen pools.

Conclusion and clinical importance: The recombinant C. obsoletus complex allergens can stimulate antigen-specific Th1 and IL10 producing Treg cells and are therefore promising candidates for the immunotherapy of IBH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology*
  • Allergens / metabolism
  • Animals
  • Cells, Cultured
  • Ceratopogonidae / metabolism*
  • Gene Expression Regulation
  • Horse Diseases / immunology*
  • Horse Diseases / metabolism
  • Horses
  • Hypersensitivity / immunology
  • Hypersensitivity / veterinary*
  • Insect Bites and Stings / immunology
  • Insect Bites and Stings / veterinary*
  • Interferon-gamma
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recombinant Proteins
  • T-Lymphocytes / metabolism*

Substances

  • Allergens
  • RNA, Messenger
  • Recombinant Proteins
  • Interferon-gamma