MODULATION OF T-CELL CYTOKINE SECRETION BY ACCESSORY CELL-DERIVED PRODUCTS

Several major pathological characteristics of atopic disease are causa lly related to CD4+ allergen-specific type 2 T-helper (Th2) cells with an aberrant cytokine secretion profile, comprising high levels of int erleukin (IL)-4 and IL-5 and low levels of interferon (IFN)-gamma. Alt hough the cytokine secretion patterns of CD4+ T-cells may be stable, t hey can be modulated by physiological factors which may be expected to be present during activation of these T-cells. In this review, we wil l focus on two secretion products of professional antigen presenting c ells (APCs) and accessory cells with opposite modulatory effects on T- cell cytokine profiles, i.e. prostaglandin E(2) (PGE(2)) and IL-12. PG E(2) favours Th2-like cytokine secretion profiles by inhibiting the pr oduction of the Th1-associated cytokines, IL-2 and IFN-gamma, and in t he presence of sufficient levels of IL-2, upregulating the production of the Th2-associated cytokines, IL-4 and IL-5. IL-12, on the other ha nd, induces and enhances IFN-gamma secretion in activated CD4+ T-cells , thereby promoting the generation of Th1 cells, PGE(2) and IL-12 act via independent mechanisms and, therefore, do not mutually interfere w ith their modulatory effects. These data suggest that the relative con tribution of PGE(2) and IL-12 to the levels of secreted Th1- and Th2-a ssociated cytokines are determined by their concentration ratio during T-cell activation.