Mechanisms of IgE tolerance: dual regulatory T cell lesions in perinatal IgE tolerance.
The mechanisms of genetic control of IgE responses are exercised at different immuno-physiological levels. This study centered upon the development of IgE lineage-specific regulatory T cells. Herein, we demonstrate the following points: (a) perinatal administration of soluble self IgE molecule or self IgE complexed with foreign antigen induces IgE tolerance as manifested by antigen-specific IgE unresponsiveness and a generalized IgE immunodeficiency, and the induction of IgE tolerance does not affect antigen-specific IgG1, IgG, and IgA responses; (b) inducibility of perinatal IgE tolerance is correlated with complete absence of endogenously secreted IgE in the neonates; and the state of persistent IgE tolerance also does not correlate with the presence of high levels of circulating anti-IgE autoantibodies; (c) The lesions induced during the ontogeny of IgE antibody system do not appear to result from an imbalance of production of interleukin 4 and interferon-gamma by T helper Th2 and Th1 cells in antigen-stimulated cultures; the dual immunoregulatory lesions in T cell subsets are demonstrated: clonal anergy/deletion of CD4+ IgE Th cells and the presence of CD8+ IgE suppressor cells induced by perinatal IgE treatment. We propose that antigen/interleukin 4 activated B cells are controlled by IgE lineage-specific regulatory T cells which recognize self IgE determinant(s) on IgE committed B cells. Life-long IgE tolerance ensues as a result of a new steady state of IgE lineage-specific CD4+ and CD8+ T cell subsets.
Department of Veterinary Science, IANL, School of Biological Sciences, University of Nebraska, Lincoln 68583-0905.
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D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis; D005260:Female; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000276:immunology*; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D016827:CD8 Antigens; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma