Administration of anti-FcER1 antibody injections daily for 10 consecutive days delays type 1 diabetes onset in NOD mice (119.11)

Abstract

Abstract Helminth infections protect against autoimmune diseases. In this study, we investigated whether mimicking the immune response induced by helminths could protect against autoimmunity in the absence of actual infection. As helminths cause chronic IgE-mediated activation of basophils and mast cells, we tested the hypothesis that continuous activation of these cells would delay the onset of diabetes in NOD mice. Twelve week old NOD mice were injected i.p. daily with 5ug of anti-FcER1 antibody or isotype control for 10 days and onset of diabetes assessed. In vitro effects of anti-FcER1 were studied by measuring IL-4 production in basophils by flow cytometry and in vivo effects were assessed by measuring plasma histamine and IL-4 levels 30 min and 18 h after i.p. injection of antibody. Cellular immune responses were evaluated by measuring cytokine production from splenocytes by ELISA and assessing frequencies of natural T and B regulatory cells by multicolor flow cytometry. Injections of anti-FcER1 resulted in release of IL-4 and histamine into the bloodstream, consistent with in vivo basophil and mast cell activation. Anti-FcER1 or isotype treatment increased production of IL-10 from splenocytes. By 20 weeks of age, 80% of mice in the control and isotype groups had developed diabetes, compared to only 20% of mice treated with anti-FcER1. These results demonstrate that anti-FcER1 therapy can delay the onset of Type I diabetes in NOD mice.