Final Activity Report Summary - NICKEL RHINITIS (Functional characteristics of allergen-specific T lymphocytes in nickel-induced allergic rhinitis) The aim of the present study was to find correlates between phenomena observed in vitro, and the clinical symptoms of nickel allergy. Additionally, we attempted to explain the factors determining that one person will react with skin inflammation, whereas another one - with rhinitis. In 40 persons with allergic contact dermatitis to nickel (Ni-ACD), we sought potential correlations between nickel-specific cytokine secretion and the outcome of patch test in the group of patients with allergic contact dermatitis to nickel. The levels of IL-5 and IFN-gamma secreted by peripheral blood lymphocytes (PBMC) in response to nickel measured with ELISA were correlated with the intensity of skin inflammation (patch test score). Additionally 19 patients with nickel-related rhinitis (Ni-Rh) and 22 patients with Ni-ACD, and 17 non-allergic volunteers were studied. The percentage of nickel-reactive cells was assessed in cells expressing CLA (skin-related homing antigen) and cells expressing HML/CD107 (mucosa-related homing antigens). Ni-specific secretion of IL-2 (naive cells), IL-13 (Th2/Tc2), and IFN-gamma (Th1/Tc1) was measured by means of ELISPOT (enzyme-linked immunospot assay). CD14+ monocytes were used as antigen presenting-cells (APC). We have demonstrated that nickel-specific IL-5 secretion by PBMC determines the intensity of patch test reaction (p=0.05) with no significant effect of IFN-gamma. An increase in the signal of IL-5 by 10 pg/ml is associated with a 24.2% increase in the predicted odds of patient being in upper category of patch test score (p=0.05). IFN-gamma had no significant influence on the odds ratio. An increase in the nickel-specific IL-5 secretion by 10 pg/ml is associated with a 10-20% increases (depending on statistical model) in the odds ratio of the patient to have a higher patch test score. This supports the assumption that cells secreting IL-5 (e.g. Th2, Tc2) play more important role in the pathogenesis of ACD than previously thought. No clear differences could be found between the cytokine secretion between the lymphocyte subpopulations (CLA+, HML-1+), and between the studied groups (patients with nickel rhinitis, Ni-ACD patients, healthy controls). We have demonstrated that the level of the allergen-specific IL-5 production is a relevant predictor of patch test score, whereas IFN-gamma is not. This supports the assumption that type 2 cells secreting IL-5 (e.g. Th2, Tc2, possibly also NK2 or NKT2) play an important (if not crucial) role in the pathogenesis of allergic contact dermatitis. We were not able to demonstrate a different cytokine response to nickel of lymphocyte subsets with different homing antigens.
