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

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Abstract
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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