Developing CD8 T cells pre-alpha TCR rearrangement support development of a unique neuronal population in the thymus 3222

Abstract Description Peripheral nervous system innervation of various organs has been associated with the development and maintenance of the immune system. Various neurological insults including brain tumors induce thymic involution. Using flow cytometry and confocal microscopy, we identified a population of cells within the thymus that contained neuronal markers and morphology. Subsets expressed tyrosine hydroxylase, BIII tubulin and/or NeuN, distinguishing them from thymic epithelial cells. These cells do not express AIRE. Neuronal cell bodies and/or axonal processes were identified within the thymus. Using retrograde rabies vector neurotracers, we confirmed axonal connections and the identity of thymic neurons. To determine developmental T cell stages that support neuronal development, we evaluated RAG1/2 KO, TCRβ KO, TCRα KO, TCRγδ KO, CD4 KO, CD8 KO and OT-I and -II transgenics. RAG1/2 and TCRβ deficiency resulted in complete loss of thymic neurons. This is while TCRα KO, TCRγδ KO, CD4/8 KO and OT-II transgenics had normal thymic neuron development. Importantly, OT-I transgenics had a significant loss of neuron-like cells, indicating developing CD8 T cells pre-alpha arrangement control thymic innervation. Finally, introduction of healthy bone marrow into irradiated RAG KO mice can restore neuron development. To summarize, we describe a novel population of neuronal cells within the thymus that interact with developing thymocytes to establish optimal thymic innervation. Funding Sources R00NS117799 Topic Categories Neuroimmunology (NEUR)