title: Modulation of T-cell cytokine secretion by accessory cell-derived products.
abstract: Several major pathological characteristics of atopic disease are causally related to CD4+ allergen-specific type 2 T-helper (Th2) cells with an aberrant cytokine secretion profile, comprising high levels of interleukin (IL)-4 and IL-5 and low levels of interferon (IFN)-gamma. Although the cytokine secretion patterns of CD4+ T-cells may be stable, they can be modulated by physiological factors which may be expected to be present during activation of these T-cells. In this review, we will focus on two secretion products of professional antigen presenting cells (APCs) and accessory cells with opposite modulatory effects on T-cell cytokine profiles, i.e. prostaglandin E2 (PGE2) and IL-12. PGE2 favours Th2-like cytokine secretion profiles by inhibiting the production of the Th1-associated cytokines, IL-2 and IFN-gamma, and in the 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 hand, induces and enhances IFN-gamma secretion in activated CD4+ T-cells, thereby promoting the generation of Th1 cells. PGE2 and IL-12 act via independent mechanisms and, therefore, do not mutually interfere with their modulatory effects. These data suggest that the relative contribution of PGE2 and IL-12 to the levels of secreted Th1- and Th2-associated cytokines are determined by their concentration ratio during T-cell activation.
authors.affiliation: University of Amsterdam, Dept of Cell Biology and Histology, The Netherlands.
authors.forename: C M
authors.initials: CM
authors.lastname: Hilkens
authors.forename: A
authors.initials: A
authors.lastname: Snijders
authors.forename: F G
authors.initials: FG
authors.lastname: Snijdewint
authors.forename: E A
authors.initials: EA
authors.lastname: Wierenga
authors.forename: M L
authors.initials: ML
authors.lastname: Kapsenberg
mesh_terms: D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000378:metabolism / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015232:Dinoprostone / Q000276:immunology / Q000502:physiology*; D015536:Down-Regulation; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism*; D018664:Interleukin-12 / Q000276:immunology / Q000502:physiology*; D007376:Interleukin-2 / Q000276:immunology / Q000502:physiology; D015847:Interleukin-4 / Q000378:metabolism*; D015848:Interleukin-5 / Q000378:metabolism*; D008213:Lymphocyte Activation; D018418:Th2 Cells / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D007376:Interleukin-2; D015848:Interleukin-5; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D015232:Dinoprostone