Genetic and environmental factors contributing to the onset of allergic disorders

Evidence has been accumulated to suggest that allergen-reactive Th2 cells p lay a triggering role in the activation and/or recruitment of IgE antibody- producing B cells, mast cells and eosinophils, the cellular triad involved in allergic inflammation. Recently, chemokines and chemokine receptors invo lved in such Th2-type response have been also defined. Th2 cells represent the polarized arm of the effector-specific responses that contribute to the protection against gastrointestinal nematodes and act as regulatory cells for chronic and/or excessive Th1-mediated responses. Th2 cells are generate d from precursor naive Th cells when they encounter the specific antigen in an IL-4-containing microenvironment. The question of how these Th2 cells a re selected in atopic patients is also unclear. Both the nature of the T ce ll receptor sig nailing provided by the allergen peptide ligand and a disre gulation of IL-4 production likely concur to determine the Th2 profile of a llergen-specific Th cells, but the genetic unbalanced IL-4 production is ce rtainly overwhelming. Some gene products selectively expressed in Th2 cells or selectively controlling the expression of IL-4 have recently been descr ibed. These findings allow to suggest that the upregulation of genes contro lling IL-4 expression and/or abnormalities of regulatory mechanisms of Th2 development and/or function may be responsible for Th2 responses against al lergens in atopic people. The increasing prevalence of allergy in developed countries suggests that environmental factors acting either before or afte r birth also contribute to regulate the development of Th2 cells and/or the ir function. The reduction of infectious diseases in early life due to incr easing vaccinations, antimicrobial treatments as well as changed lifestyle are certainly important in influencing the individual outcome in the Th res ponse to ubiquitous allergens. Moreover, the recent evidence that bacterial DNA or oligodeoxynucleotides containing unmethylated 'CpG motifs' promote the development of Th1 cells via the production of immunomodulatory cytokin es (namely IL-12, IL-18 and IFNs) by professional antigen-presenting cells confirms previous epidemiological data. The new insight into the pathophysi ology of T cell responses in atopic diseases provides exciting opportunitie s for the development of novel immunotherapeutic strategies. Copyright (C) 2000 S. Karger AG, Basel.