Abstract
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 IgG~1~, 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 interfron‐γ by T helper T~h~2 and T~h~1 cells in antigen‐stimulated cultures; the dual immunoregulatory lesions in T cell subsets are demonstrated: clonal anergy/deletion of CD4^+^ IgE T~h~ 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.