C Alexander1, S Ying, A B Kay, M Larché. 1. Allergy & Clinical Immunology, Faculty of Medicine, Imperial College London, London, UK.
Abstract
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.
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.
Authors: Anu K Immonen; Antti H Taivainen; Ale T O Närvänen; Tuure T Kinnunen; Soili A Saarelainen; Marja A Rytkönen-Nissinen; Tuomas I Virtanen Journal: Immunology Date: 2007-01 Impact factor: 7.397