title: Regulation of IgE synthesis by T cells and cytokines.
abstract: Human IgE synthesis is tightly regulated by cytokines. IgE production by normal B cells is specifically induced by IL-4, but requires additional, yet to be defined, signals that are provided by CD4+ T cells. Single surface IgM+ B cells can be induced to proliferate and switch to IgG4 and IgE producing cells, indicating that the induction of IgE synthesis by IL-4 and CD4+ T cells reflects direct isotype switching. Although IL-4 is the sole inducing cytokine of IgE synthesis known thus far, multiple cytokines modulate IL-4 induced IgE synthesis in vitro. IFN-alpha, IFN-gamma TGF-beta and IL-10 are inhibitory, whereas IL-5, IL-6 and TNF-alpha act synergistically with IL-4. Results obtained with animal models, as well as from clinical studies in the human have indicated that IL-4, IFN-alpha and IFN-gamma are operational in vitro. Cocultivation of B cells with allergen-specific CD4+ T cell clones producing high levels of IL-4 and IL-5, but normal to undetectable levels of IL-2 and IFN-gamma, following activation resulted in the synthesis of IgE, in the absence of exogenously added IL-4. These results indicate that aberrant ratio's of IL-4 and IFN-gamma production are sufficient for induction of IgE synthesis in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Human Immunology, DNAX Research Institute, Palo Alto, CA 94304.
authors.forename: H
authors.initials: H
authors.lastname: Yssel
authors.forename: G
authors.initials: G
authors.lastname: Aversa
authors.forename: J
authors.initials: J
authors.lastname: Punnonen
authors.forename: B
authors.initials: B
authors.lastname: Cocks
authors.forename: J E
authors.initials: JE
authors.lastname: de Vries
mesh_terms: D016207:Cytokines / Q000502:physiology*; D007073:Immunoglobulin E / Q000096:biosynthesis*; D016176:T-Lymphocyte Subsets; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*
chemical_list: D016207:Cytokines; D007073:Immunoglobulin E