Inhibition of T-cell activation by neuron and astrocytes

초록

Various immune cells are involved in neuro-inflammation after brain injury like stroke. Astrocytes can protect neurons and interact with T cells to play an important role in brain inflammation. However, it is difficult to study how T cells interact with astrocytes or neurons in vivo due to the restricted number of T cells in brain tissues. Therefore, we set a co-culture system in vitro analyzing brain cell-mediated T cell activation. Neurons and astrocytes were isolated from embryo and new born mice, respectively and co-cultured with lymphocytes in the presence of anti-CD3/CD28 antibodies which can activate T cells. Both neurons and astrocytes decreased the production of IL-4, IL-13, IL-17A, and IFN-γ cytokines in the culture media. Astrocytes especially induced IL-6 expression and inhibited IFN-γ expression more than neurons did. We observed increased production of indoleamine 2,3-dioxygenase (IDO) and inducible nitric oxide synthase (iNOS) in lymphocytes co-cultured only with astrocytes. IFN-γ expression was fully restored in the presence of IDO and iNOS inhibitor. Overall neurons and astrocytes can inhibit T-cell activation, however, the inhibitory factor(s) seems to be slightly different between two brain cells. Taken together, healthy neurons and astrocytes can inhibit the T cell activation. Probably loss of brain cells such as stroke could not inhibit T cell activation anymore which may result in the brain inflammatory diseases. The detailed molecular mechanisms of how astrocytes and neurons affect T cell signaling cascade need to be studied in future.