Regulation of IgE synthesis by T cells and cytokines. 1993

H Yssel, and G Aversa, and J Punnonen, and B Cocks, and J E de Vries
Department of Human Immunology, DNAX Research Institute, Palo Alto, CA 94304.

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)

UI MeSH Term Description Entries
D007073 Immunoglobulin E An immunoglobulin associated with MAST CELLS. Overexpression has been associated with allergic hypersensitivity (HYPERSENSITIVITY, IMMEDIATE). IgE
D006377 T-Lymphocytes, Helper-Inducer Subpopulation of CD4+ lymphocytes that cooperate with other lymphocytes (either T or B) to initiate a variety of immune functions. For example, helper-inducer T-cells cooperate with B-cells to produce antibodies to thymus-dependent antigens and with other subpopulations of T-cells to initiate a variety of cell-mediated immune functions. Helper Cell,Helper Cells,Helper T Cell,Helper-Inducer T-Lymphocytes,Inducer Cell,Inducer Cells,T-Cells, Helper-Inducer,T-Lymphocytes, Helper,T-Lymphocytes, Inducer,Helper T-Cells,Cell, Helper T,Cells, Helper T,Helper Inducer T Lymphocytes,Helper T Cells,Helper T-Cell,Helper T-Lymphocyte,Helper T-Lymphocytes,Helper-Inducer T-Cell,Helper-Inducer T-Cells,Helper-Inducer T-Lymphocyte,Inducer T-Lymphocyte,Inducer T-Lymphocytes,T Cell, Helper,T Cells, Helper,T Cells, Helper Inducer,T Lymphocytes, Helper,T Lymphocytes, Helper Inducer,T Lymphocytes, Inducer,T-Cell, Helper,T-Cell, Helper-Inducer,T-Cells, Helper,T-Lymphocyte, Helper,T-Lymphocyte, Helper-Inducer,T-Lymphocyte, Inducer
D016176 T-Lymphocyte Subsets A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells. T-Cell Subset,T-Cell Subsets,T-Lymphocyte Subset,Subset, T-Cell,Subset, T-Lymphocyte,Subsets, T-Cell,Subsets, T-Lymphocyte,T Cell Subset,T Cell Subsets,T Lymphocyte Subset,T Lymphocyte Subsets
D016207 Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Cytokine

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