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

Background Specific immunotherapy with whole allergen extracts is associated with local accumulation of IFN-gamma(+) 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-gamma(+) (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.