SKIN-HOMING, CLA(-CELLS ARE ACTIVATED IN ATOPIC-DERMATITIS AND REGULATE IGE BY AN IL-13-DOMINATED CYTOKINE PATTERN - IGG4 COUNTERREGULATIONBY CLA(-) MEMORY T-CELLS() MEMORY T)

Cutaneous lymphocyte-associated Ag (CLA) is a skin-homing receptor dis played by memory/effector T cells recognizing skin-related allergens. Here we demonstrate that peripheral blood CLA(+) CD45RO(+) T cells in patients with atopic dermatitis (AD) are in vivo activated. They spont aneously proliferate and release an IL-13-dominated Th2 cytokine profi le and are capable of inducing IgE in autologous B cells without furth er activation. The spontaneous cytokine release occurred within the fi rst hour of culture and was not inhibited by cycloheximide or by other immunosuppressive drugs, indicating that cytokine transcription and t ranslation had been completed in vivo. In contrast, the CLA-CD45RO(+) T cells from the same patients and from nonatopic controls represented a resting memory T cell subset, secreted borderline quantities of cyt okines, and induced IgG4. Polyclonal activation by the anti-CD2/anti-C D3/anti-CD28 mAb mixture generated distinct cytokine patterns in the t wo memory/effector T cell subsets. CLA(+) T cells secreted Th2 cytokin es with high IL-13 levels, and the CLA(-) subset mainly produced IFN-g amma. There was no difference in in vitro activated cytokine pattern b etween AD patients and nonatopic subjects. These results indicate that the CLA(+) memory/effector T cells of AD patients are activated in vi vo and play a pivotal role in allergic inflammation by production of I L-13 and induction of IgE Abs. In contrast, the CLA-resting memory T c ell population may exert immunoprotective properties toward allergen b y high IFN-gamma secretion and induction of IgG4.