Intermittent Ca2+ signals mediated by Orai1 regulate basal T cell motility

To help protect the body from disease, small immune cells called T lymphocytes move rapidly, searching for signs of infection. These signs are antigens – processed pieces of proteins from invading bacteria and viruses – which are displayed on the surface of so-called antigen-presenting cells. To visit as many different antigen-presenting cells as possible, T cells move quickly from one to the next in an apparently random manner. How T cells are programmed to move in this way is largely unknown. The entry of calcium ions into cells triggers characteristic actions in many cells throughout the body. In T cells, calcium ions enter through Orai1 proteins that form calcium channels on the cell surface. Now, Dong, Othy et al. have asked whether calcium signals guide moving T cells as they search for antigens. Experiments with individual human T cells in small tubes showed that blocking the Orai1 calcium channels caused the T cells to move faster, because the cells paused less often. The same was seen when human T cells were transplanted into mice. These findings suggested that calcium signals may indeed guide the T cells’ movement, but actually being able to see the calcium signals in the cell would give a much clearer picture of what goes on. To achieve this, Dong, Othy et al. report, in a related study, how they genetically engineered mice to produce a calcium-sensitive reporter protein in their T cells. Using these new transgenic mice, Dong, Othy et al. could see calcium signals in the T cells before each of the T cell’s pauses. Further experiments showed that the calcium signals that control the cell’s movements are triggered both by contact with the antigen-presenting cells and internally within the T cells themselves. In another related study, Guichard et al. also conclude that contact with antigen-presenting cells causes calcium signals that control the responses of T cells. Seemingly random patterns of movement help T cells search for signs of infection, and these new findings reveal a basic part of how T cells are programmed to move in this way. A deeper understanding of T cell movement might allow this process to be controlled. In particular, this knowledge could lead to new treatments for autoimmune diseases, in which T cells incorrectly recognize the body’s own antigens as signs of an infection.