Neurons Induce Exhausted CD73+ CD8+ T-Cell Phenotypes to Suppress Inflammatory Responses

초록

The brain is known to be an immune-privileged organ where adaptive immunity and inflammation are highly regulated. Various immune cells infiltrate and trigger nerve cell death when the brain is damaged. T cells play a crucial role in brain inflammation. However, the regulation of T cells by brain cells has not been thoroughly studied. This study investigated how neurons regulate T cells during TCR signaling using a neuron-lymphocyte co-culture system in vitro. Primary cortical neurons were isolated from fetal brains at 13-14 days of gestation and cultured for one week. Lymphocytes were isolated from the spleen and lymph nodes and co-cultured with neurons in the presence of anti-CD3/CD28 antibodies. Subsequently, T-cell activations were observed. Interestingly, effector cytokines such as IFN-?, IL-4, IL-17A, IL-6, and IL-13 were decreased by neurons, while CD44hi CD62Llo effector phenotype T cells were increased. Neurons have a significant impact on CD8 T cells. In addition, increased PD-1, Tim-3, and CD73 expressions and decreased granzyme B expression were observed in CD8 T cells in the presence of neurons. SB431542, a TGF-?-pathway inhibitor, restored all of these phenotypes. Our research suggests that neurons can induce exhausted T-cell phenotypes, and these immunosuppressive functions of neurons may be mediated by TGF-? pathways. This critical insight into the role of TGF-? pathways in neuron-mediated T-cell suppression could have significant implications for future research and therapeutic development of brain diseases or cancer.