844 Environmental Factors Favoring the Allergen- specific Th2 Response in Allergic Subjects MARIE-PIERRE PICCINNI, a ENRICO MAGGI, AND SERGIO ROMAGNANI Department of Internal Medicine, Immunoallergology Unit, University of Florence, 85 viale Morgagni, 50134 Florence, Italy ABSTRACT: Allergen-reactive type 2 helper T cells (Th2) play a triggering role in the activation and/or recruitment of IgE antibody-producing B cells, mast cells, and eosinophils, i.e., the cellular triad involved in the allergic inflamma- tion. Interleukin (IL)-4 production at the time of antigen presentation to the Th cell is critical for the development of Th2 cells. Other cytokines, such as IL-1 and IL-10, and hormones, such as calcitriol and progesterone, also play a positive role. In contrast, cytokines such as interferon (IFN)- , IFN-, IL-12, and transforming growth factor (TGF)- , and relaxin play a negative regula- tory role on the development of Th2 cells. However, the mechanisms underly- ing the preferential activation by environmental allergens of Th2 cells in atopic individuals still remain obscure. Some gene products selectively expressed in Th2 cells or selectively controlling the expression of IL-4 have recently been described. Moreover, cytokines and other gene products that dampen the pro- duction of IL-4, as well as the development and/or the function of Th2 cells, have been identified. These findings allow us to suggest that the upregulation of genes controlling IL-4 expression and/or abnormalities of regulatory mech- anisms of Th2 development and/or function may be responsible for Th2 responses against common environmental allergens in atopic subjects. INTRODUCTION Atopy is a genetically determined group of disorders characterized by an increased ability of B lymphocytes to synthesize IgE antibodies against ubiquitous antigens (allergens) able to activate the immune system after inhalation or ingestion, and per- haps after penetration through the skin. IgE antibodies are able to bind to high-affinity Fcε receptors (FcεRI) present on the surface of mast cells/basophils, and allergen- induced FcεRI cross-linking triggers the release of vasoactive mediators, chemotactic factors, and cytokines that are responsible for the allergic events. In addition, eosino- phils also appear to be involved in the pathogenesis of allergic reactions because they usually accumulate at the site of allergic inflammation, and their toxic products significantly contribute to tissue damage. The mechanisms linking IgE-producing B cells, mast cells/basophils, and eosino- phils in the pathogenesis of allergic reactions have remained unclear until distinct subsets of CD4+ T helper (Th) cells, based on their profile of cytokine secretion, were a Address for correspondence: Dr. Marie-Pierre Piccinni, Dipartimento di Medicina Interna- sezione: Immunoallergologia, Viale Morgagni, 85, Firenze 50134, Italy. Voice: +39-055-4271353; fax: +39-055-412867. mppiccinni@hotmail.com