Induction of exhausted CD8 T cells by primary cortical neurons 2617

Abstract Description The brain is recognized as an immune-privileged organ where adaptive immunity and inflammation are tightly regulated. Various immune cells infiltrate the brain and can induce neuronal cell death when damage occurs. T cells play a critical role in brain inflammation; however, the regulation of T cells by brain cells has yet to be extensively studied. This study investigated how neurons regulate T-cell activation. Primary cortical neurons were isolated and co-cultured with lymphocytes in the presence of anti-CD3/CD28 antibodies. Interestingly, effector cytokines such as IFN-γ, IL-4, IL-17A, IL-6, and IL-13 were found to be decreased by neurons, while the population of CD44hi CD62Llo effector phenotype T cells increased. Neurons significantly impacted CD8 T cells. Additionally, increased PD-1, Tim-3, and CD73 expression levels and decreased Granzyme B expression were observed in CD8 T cells in the presence of neurons. A TGF-β pathway inhibitor SB431542 restored all of these phenotypes. These exhausted CD8 T cells exhibited reduced cytotoxicity against B16F10 melanoma cells, which SB431542 also restored. Our research indicates that neurons can induce exhausted T-cell phenotypes and that TGF-β pathways may mediate neurons’ immunosuppressive functions. This critical insight into the role of TGF-β pathways in neuron-mediated T-cell suppression could have significant implications for future research and the therapeutic development of neurological disorders and cancer. Funding Sources NRF-2017M3C7A1031108, NRF-2022R1A2C1010354 Topic Categories Neuroimmunology (NEUR)