When do thymocytes perceive IFN signaling during development? 2485

Abstract Description T cells need to be tolerant to self in both homeostatic and inflammatory contexts, like type I IFN mediated inflammation. In the thymus, type I IFNs are constantly produced in a sterile manner, which activates APC and enables presentation of peptides derived from interferon stimulated genes (ISG). Thymocytes also possess the machinery to sense type I IFN, thus we reasoned that IFNs may play a role in their maturation. To test this, thymocytes that report IFN sensing by expressing GFP from the locus of the ISG Mx1 (Mx1GFP) were analyzed. We found that SP thymocytes, albeit a small percentage, were GFP+ at steady state. This low percentage was surprising since other ISG, Qa-2 and Ly6A, were expressed in the majority of SP thymocytes and naïve T cells. We hypothesize that most SP sense IFN at some point in their maturation but are only transiently positive in Mx1GFP mice. To address this, we developed a mouse model, Mx1CreERT2RosaLsltomato, which will permanently mark IFN signaled cells (tomato+) through Mx1 dependent Cre recombinase activity. The combination of the Mx1CreERT2RosaLsLTomato with Mx1GFP mouse models will allow us to describe the history of IFN perception and better understand its role in developing and naïve T cells. Topic Categories Hematopoiesis and Immune System Development (HEM)