C A Akdis1, M Akdis, H U Simon, K Blaser. 1. Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland. akdisac@siaf.unizh.ch
Abstract
BACKGROUND: In allergic inflammations of the skin, the pivotal role of CD45RO+ (memory/effector) T cells expressing the cutaneous lymphocyte-associated antigen (CLA) was demonstrated. In both atopic dermatitis (AD) and contact dermatitis (CD), T cells specific to skin-related allergens were confined to the CLA+ T cell population. Our research was aimed to further characterize these T cells in AD. METHODS: CD4+ and CD8+ subsets of CLA+ CD45RO+ T cells were purified from peripheral blood of AD patients and healthy control individuals. We studied, in vivo activation patterns, cytokine profiles, immunoglobulin isotype regulation and the influence of these cells on eosinophil survival and apoptosis. RESULTS: The CLA+ CD45RO+ T cells represent an in- vivo-activated memory/effector T cell subset as shown by surface expression of activation markers, spontaneous proliferation and a lower activation threshold via TCR/CD3 triggering. These cells contain and spontaneously release high amounts of preformed IL-5 and IL-13 but only very little IL-4 and IFN-gamma in their cytoplasm, as demonstrated by intracellular cytokine staining immediately after purification. Moreover, CLA+ memory/ effector T cells induce IgE production in B cells and enhance eosinophil survival by inhibiting eosinophil apoptosis in AD. In comparison, the CLA- population represents a resting memory T cell fraction, induces rather IgG4 in B cells and does not show any effect on eosinophil survival and apoptosis. CONCLUSION: Our results indicate that in-vivo-activated both CD4+ and CD8+ memory/effector T cells with skin-homing property play a specific and decisive role in the pathogenesis and exacerbation of AD. In contrast, resting memory T cells of atopic individuals retain normal, nonallergic immune functions.
BACKGROUND: In allergic inflammations of the skin, the pivotal role of CD45RO+ (memory/effector) T cells expressing the cutaneous lymphocyte-associated antigen (CLA) was demonstrated. In both atopic dermatitis (AD) and contact dermatitis (CD), T cells specific to skin-related allergens were confined to the CLA+ T cell population. Our research was aimed to further characterize these T cells in AD. METHODS:CD4+ and CD8+ subsets of CLA+ CD45RO+ T cells were purified from peripheral blood of ADpatients and healthy control individuals. We studied, in vivo activation patterns, cytokine profiles, immunoglobulin isotype regulation and the influence of these cells on eosinophil survival and apoptosis. RESULTS: The CLA+ CD45RO+ T cells represent an in- vivo-activated memory/effector T cell subset as shown by surface expression of activation markers, spontaneous proliferation and a lower activation threshold via TCR/CD3 triggering. These cells contain and spontaneously release high amounts of preformed IL-5 and IL-13 but only very little IL-4 and IFN-gamma in their cytoplasm, as demonstrated by intracellular cytokine staining immediately after purification. Moreover, CLA+ memory/ effector T cells induce IgE production in B cells and enhance eosinophil survival by inhibiting eosinophil apoptosis in AD. In comparison, the CLA- population represents a resting memory T cell fraction, induces rather IgG4 in B cells and does not show any effect on eosinophil survival and apoptosis. CONCLUSION: Our results indicate that in-vivo-activated both CD4+ and CD8+ memory/effector T cells with skin-homing property play a specific and decisive role in the pathogenesis and exacerbation of AD. In contrast, resting memory T cells of atopic individuals retain normal, nonallergic immune functions.