ANALYSIS OF T-CELL ACTIVATION AFTER BRONCHIAL ALLERGEN CHALLENGE IN PATIENTS WITH ATOPIC ASTHMA

Background: T helper cells are a heterogeneous group of cells that hav e phenotypic and functional differences. Activated T helper cells have been found in peripheral blood after allergen challenge of subjects w ith atopic asthma, but the phenotypes of specific T helper subpopulati on involved remains to be identified. Objective: To characterize the T cell activation markers that may be regulated by allergens, we analyz ed peripheral blood lymphocytes obtained before and after allergen cha llenge from subjects with atopic asthma. Methods: We analyzed the dist ribution of the cell surface activation markers, interleukin 2 recepto r (IL-2R) and major histocompatibility complex class Ii antigens (MHC II) among T helper subpopulations classified as naive (CD45RA) or memo ry (CD45RO) phenotypes. Nine adult subjects with atopic asthma underwe nt bronchoprovacative allergen inhalation and isocapnic cold air hyper ventilation (ISH) challenge followed by serial spirometry. Peripheral blood mononuclear cells (PBMC) were isolated at baseline and 2 and 24 hours after challenge. Four color how cytometry was used to analyze th e expression and distribution in vivo of IL-2R and MHC LI activation m arkers on naive and memory T cell subsets after challenge. Results: At 2 and 24 hours after allergen challenge, there was a significant incr ease in the CD45RO+IL-2R+ T helper cells compared with baseline (mean +/- SE, baseline, 12.5% +/- 1% versus 2 hours, 18.1% +/- 1% and 24 hou rs, 17.8% +/- 2%, p < 0.025). MHC II expression was not significantly increased after challenge on naive and memory T helper cells and coexp ression of IL-PR and MHC II was only found in a small proportion of CD 45RO+ T helper cells (2.7% +/- 1%). No changes of IL-2R or MBC II expr ession on T helper subsets were observed after ISH challenge in the sa me patients. We also found that 31% to 46% of T helper cells coexpress CD45RA and CD45RO simultaneously, and upregulation of IL-2-R and MHC II expression occurs only on those T helper cells that express CD45RO. Conclusions: We have found that T helper cells express both CD45RA an d CD45RO isoforms, which suggests the existence of a transitional phen otype among naive and memory T helper cells in peripheral blood. In su bjects with atopic asthma, our in vivo analysis characterizes two popu lations of activated memory T helper cells based on the expression of IL-2R or MHC II surface molecules after allergen challenge.