T cells and their role in allergies.
The molecular and cellular mechanisms which up-regulate IgE synthesis in most atopic patients are only incompletely understood. There is no doubt that T cells play a prominent role in the B cell immunoglobulin switch to IgE. T-cell-derived interleukin (IL)-4 is a specific inducer of IgE synthesis which activates B cells to proliferate and, furthermore, induces other cells to release cytokines which enhance IgE synthesis. Additional costimulatory signals are required, however, for B cell activation and the consequent immunoglobulin switch to IgE. Besides physical B/T cell interaction, direct B cell activation through anti-CD40 provides such a signal. IL-4-induced B cell activation is amplified by other cytokines such as IL-5, IL-6, IL-3, probably IL-9, and tumor necrosis factor-alpha, whereas interferon (IFN)-gamma, IFN-alpha, transforming growth factor-beta and IL-12 are able to inhibit IL-4-induced IgE synthesis. These different IgE-synthesis-modulating lymphokines are secreted by different T cell subsets, TH1 and TH2. While IgE synthesis is activated by TH2-derived lymphokines, TH1 cell clones exhibit cytolytic activity. The detection of allergen-specific T cells in peripheral blood mononuclear cells (PBMNCs) of atopic patients, with a lymphokine profile similar to TH2, and the predominance of TH2 cells in PBMNCs of these patients might be one explanation for increased serum IgE concentrations in atopic individuals. It is not known, however, which stimulus leads to a predominant expression of TH2 cells over TH1 cells in atopic patients with consequently increased IgE synthesis.
Wilhelm
D
D
Institute of Immunology and Transfusion Medicine, University of Lübeck, FRG.
Kirchner
H
H
D001402:B-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000209:etiology* / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis; D008211:Lymphocyte Cooperation / Q000276:immunology; D008954:Models, Biological; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D016207:Cytokines; D007073:Immunoglobulin E