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Clinical & Experimental Allergy

Fel d 1-derived T cell peptide therapy induces recruitment of CD4+CD25+; CD4+ interferon-γ+ T helper type 1 cells to sites of allergen-induced late-phase skin reactions in cat-allergic subjects

Authors


Mark Larché, Allergy & Clinical Immunology, Faculty of Medicine, Imperial College London, Dovehouse Street, London SW3 6LY, UK. E-mail: m.larche@imperial.ac.uk

Summary

Background Specific immunotherapy with whole allergen extracts is associated with local accumulation of IFN-γ+ and CD25+ cells indicating recruitment of activated T-helper type 1 (Th1) and/or T regulatory cells. We have studied allergen-induced, late-phase skin biopsies before and after T cell peptide therapy for evidence of alterations in the pattern of local recruitment of Th1, T-helper type 2 (Th2) and T regulatory cells.

Objective To evaluate the effect of T cell peptide therapy on the allergen-induced cutaneous late-phase reaction.

Methods Increasing doses of synthetic Fel d 1-derived peptides were administered (by intradermal injection) to eight cat-allergic asthmatics at 14-day intervals. Twenty-four-hour skin biopsies were taken from whole cat allergen- and diluent-injected sites, before and after treatment and studied by immunohistochemistry and in situ hybridization.

Results Fel-d 1 peptides decreased airway hyper-responsiveness (P=0.02) and inhibited the late-phase cutaneous reaction (LPCR) to whole cat allergen (P=0.03). This was associated with significant increases (post- vs. pre-treatment) in the number of cutaneous CD4+/IFN-γ+ (P=0.03) and CD4+/CD25+ cells (P=0.04), but not in CD4+/IL-10+ or CD4+/CTLA-4+ cells.

Conclusions Treatment with allergen-derived T cell peptides results in allergen-dependent recruitment to the skin of Th1, rather than T regulatory cells, to cutaneous late-phase reaction sites.

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