Impact of thymic interferons on T cell tolerance 4170

Abstract Description Thymic selection ensures a self-tolerant T cell repertoire. Developing T cells interact with thymic APCs presenting self-antigens and reactive clones are eliminated or induced to a Treg fate. However, peripheral APCs radically change their displayed self-antigens during infections due to inflammation induced changes in antigen processing and presentation abilities. Repeated occurrences of inflammation could therefore trigger autoimmunity if T cells were not completely tolerant to inflammation induced self-antigens. We hypothesize that production of type I and III interferons occurs in the thymus at a steady state to tolerize T cells to inflammation-induced self-antigens, allowing T cells to function during infection without raising autoimmunity. CFSE-labeled CD4 T cells from WT and type I IFN deficient (Ifnβ-/- ) mice did not show differences in self-reactivity when adoptively transferred into resting B6 mice. However, if recipient mice were injected with polyI:C prior to transfer, T cells from Ifnβ-/- mice showed increased proliferation. This suggests that thymic IFNβ exposure tolerizes T cells to inflammation induced self-antigens. To further test this idea, we created a thymic type I&III IFN deficient mouse model by grafting the thymus from an Ifnβ/Ifnλ knockout mouse onto the kidney capsule of Foxn1 nude recipient mice. We will age these mice to monitor autoimmune pathologies by measuring effector memory T cell increase, increased autoantibodies, and tissue infiltration. Funding Sources R01 AI179749 Topic Categories Basic Autoimmunity (BA)