A molecular basis for T cell suppression by IL‐10: CD28‐associated IL‐10 receptor inhibits CD28 tyrosine phosphorylation and phosphatidylinositol 3‐kinase binding

Abstract

SPECIFIC AIMthe present study demonstrates that interleukin 10 (IL-10) induces T cell tolerance in natural high-dose antigen exposure and specific immunotherapy by blocking the CD28 pathway, and thus inhibits T cells stimulated by low numbers of triggered T cell receptors that require costimulation.PRINCIPAL FINDINGS1. IL-10 induces T cell tolerance in natural high-dose antigen exposure and specific immunotherapyPeripheralT cell tolerance is induced in subjects naturally receiving high antigen loads as well as in specific immunotherapy of allergy. During the course of specific immunotherapy, the T cell proliferative response to major antigen is significantly suppressed in parallel to IL-4, IL-5, IL-13, and interferon γ (IFN-γ) production. Simultaneously with the specific suppression of the T cells, the antigen-induced secretion of IL-10 increased within 7 days. The same features of T cell suppression with increased IL-10 production were detected in individuals who received high doses of antigens (i.e., mu...