REVERSAL OF HUMAN ALLERGIC T-HELPER 2 RESPONSES BY ENGAGEMENT OF SIGNALING LYMPHOCYTIC ACTIVATION MOLECULE

Allergen-specific Th2 cells accumulate at high frequencies in the skin of patients with atopic dermatitis (AD), where they contribute to the induction and maintenance of the lesions that are characteristic for the disease, Attenuation of these lesions in response to successful th erapy is associated with a reduction in IL-4-producing Th2 cells and t he appearance of IFN-gamma-producing producing Th cells, In this study , we demonstrate that engagement of the signaling lymphocytic activati on molecule (SLAM) by an agonistic mAb, during allergen-specific expan sion of highly polarized Th2 cell populations derived from skin biopsi es of AD patients, results in the generation of stable populations of IFN-gamma-producing cells, SLAM-mediated reversal of Hh cell phenotype has important biologic consequences, because supernatants of these ac tivated, allergen-specific Th cells fail to induce IgE synthesis by pu rified B cells costimulated by anti-CD40 mAbs, Thus, highly polarized, allergen-specific Th2 cell populations derived from the skin of AD pa tients can be reversed into Th cell populations that contain IFN-gamma -producing cells and that do not support IgE synthesis. These results define a new mechanism to promote th0/Th1 differentiation and suggest a potential role for anti-SLAM mAbs in the treatment of Th2-mediated a llergic diseases.