Production and Modulation of T-Cell Cytokines in Atopic Allergy

Atopic allergy is associated with allergen-specific CD4+ T cells showing a bias to production of the type-2 cytokines interleukin (IL)-4 and IL-5. There are indications that this bias is also evident in atopic T-helper (Th) cells with other antigen specificities. The balance between the production of type-1 and type-2 cytokines is influenced by various factors present in the microenvironment of the Th cells during their activation. Factors of special interest are antigen-presenting cell-derived IL-12 and prostaglandin E2, skewing to type-1 and type-2 cytokine production, respectively. The production of IL-12 and prostaglandin E2 is induced by the interaction between CD40 and CD40 ligand expressed by Th cells, and by biologically active agents such as micro-organisms or their products. The IL-12/prostaglandin E2 production ratio depends on the antigen-presenting cell type, the type of stimulus and the presence of certain cytokines. Other Th-cytokine-skewing factors are autocrine or paracrine IFN-gamma and IL-4. In fact, the type-1/type-2 cytokine production balance in Th cells is under the control of various soluble products that act in a complex network of type-1 (e.g. IL-12, IFN-gamma) or type-2 (e.g. IL-4, IL-10 and prostaglandin E2) factors and are produced by Th cells and their accessory antigen-presenting or bystander cells. The levels of these factors may further be determined by gene polymorphisms or aberrant hormone levels. Despite the growing knowledge of the regulation of Th-cell cytokine production, the etiology of biased cytokine production in atopic allergic individuals is still enigmatic.