Abstract
In order to determine the potential for allergen to modulate T cell expression of the CysLT1 receptor and responsiveness to leukotrienes, peripheral blood mononuclear cells from house dust mite-allergic or nonallergic individuals were incubated with D. pteronyssinus allergen (Der p). Baseline CysLT1 expression was similar in both groups of donors, but Der p significantly enhanced CysLT1 expression in CD4+ and CD8+ T cells of only allergic individuals and induced enhanced responsiveness of CD4+ T cells to LTD4 in terms of calcium mobilisation. This effect was prevented by the CysLT1 antagonist MK571. Der p also induced IL-4 and IL-10 production, and neutralizing antibody to IL-4 prevented both the enhanced CysLT1 expression and the enhanced responsiveness of T cells to LTD4 induced by Der p. In allergic individuals, Der p also induced T cell proliferation and a Th2-biased phenotype. Our data suggest that, in allergen-sensitized individuals, exposure to allergen can enhance T cell expression of CysLT1 receptors through a mechanism involving IL-4 production. This, in turn, would induce CD4+ T cell responsiveness to cysteinyl-leukotrienes and Th2 cell activation.
Highlights
Cysteinyl-leukotrienes, leukotriene C4, LTD4, and LTE4, are lipid mediators of inflammation well known to be involved in the pathogenesis of asthma and the resulting pulmonary inflammation [1]
The present study demonstrated that the Dermatophagoides pteronyssinus (Der p) allergen ianndduCceDd8a+nTinccerlelsasferdomexHprDesMsio-anlloefrgCiycssLuTb1jercetcse,pwtohrerineaCs DD4e+r p had no significant effects on T cells from non-HDMallergic individuals
This upregulation of CysLT1 expression by Der p induced an enhanced responsiveness of T cells to LTD4
Summary
Cysteinyl-leukotrienes (cysLTs), leukotriene C4, LTD4, and LTE4, are lipid mediators of inflammation well known to be involved in the pathogenesis of asthma and the resulting pulmonary inflammation [1] They are mainly produced by eosinophils, mast cells, basophils, monocytes, macrophages, and dendritic cells (DC) from arachidonic acid through the 5-lipoxygenase pathway [2]. CysLT1, recognized as the high-affinity receptor for LTD4, is expressed mainly in peripheral blood leukocytes, including eosinophils, monocytes, neutrophils, basophils, DC, B lymphocytes, and T cells, as well as in mast cells, interstitial lung macrophages, and bronchial smooth muscle cells [7,8,9,10,11,12,13]. CysLTs have been found to promote cytokine and chemokine expression in various cellular models and IgE production by human B cells [15, 18,19,20,21]
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