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Eur J Immunol. 2016 Jan;46(1):242-52. doi: 10.1002/eji.201545869. Epub 2015 Nov 17.

Elevated and cross-responsive CD1a-reactive T cells in bee and wasp venom allergic individuals.

Author information

1
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine and University of Oxford, NIHR Biomedical Research Centre, Oxford, England, UK.
2
Section of Musculoskeletal Disease, University of Leeds, Leeds, UK.
3
Department of Clinical Immunology, Oxford University Hospitals NHS Trust, Oxford, UK.
4
Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Abstract

The role of CD1a-reactive T cells in human allergic disease is unknown. We have previously shown that circulating CD1a-reactive T cells recognize neolipid antigens generated by bee and wasp venom phospholipase, and here tested the hypothesis that venom-responsive CD1a-reactive T cells associate with venom allergy. Circulating T cells from bee and wasp venom allergic individuals, before and during immunotherapy, were exposed to CD1a-transfected K562 cells in the presence of wasp or bee venom. T-cell response was evaluated based on IFNγ, GM-CSF, and IL-13 cytokine production. Venom allergic individuals showed significantly higher frequencies of IFN-γ, GM-CSF, and IL-13 producing CD1a-reactive T cells responsive to venom and venom-derived phospholipase than healthy individuals. Venom-responsive CD1a-reactive T cells were cross-responsive between wasp and bee suggesting shared pathways of allergenicity. Frequencies of CD1a-reactive T cells were initially induced during subcutaneous immunotherapy, peaking by weeks 5, but then reduced despite escalation of antigen dose. Our current understanding of venom allergy and immunotherapy is largely based on peptide and protein-specific T cell and antibody responses. Here, we show that lipid antigens and CD1a-reactive T cells associate with the allergic response. These data have implications for mechanisms of allergy and approaches to immunotherapy.

KEYWORDS:

CD1a-reactive T cells; Immunotherapy; Phospholipase; Venom allergy

Comment in

PMID:
26518614
PMCID:
PMC4738458
DOI:
10.1002/eji.201545869
[Indexed for MEDLINE]
Free PMC Article

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