Quantitative analyses of T cell motion in tissue reveals factors driving T cell search in tissues

Abstract

AbstractT cells are required to clear infection, moving first in lymph nodes to interact with antigen bearing dendritic cells leading to activation. T cells then move to sites of infection to find and clear infection. T cell motion plays a role in how quickly a T cell finds its target, from initial naïve T cell activation by a dendritic cell to interaction with target cells in infected tissue. To better understand how different tissue environments might affect T cell motility, we compared multiple features of T cell motion including speed, persistence, turning angle, directionality, and confinement of motion from T cells moving in multiple tissues using tracks collected with two-photon microscopy from murine tissues. We analyzed naïve CD8 T cells moving within the lymph node with activated CD8 T cells moving within the villi of small intestine and lung under different activation conditions.Our analysis found that while the speeds and the overall displacement of T cells vary within all tissues analyzed, T cells in all tissues tended to persist at the same speed, particularly if the previous speed is very slow (less than 2 μm/min) or very fast (greater than 8 μm/min). Interestingly, we found that turning angles of T cells in the lung show a marked population of T cells turning at close to 180°, while T cells in lymph nodes and villi do not exhibit this “reversing” movement. Additionally, T cells in the lung showed significantly decreased meandering ratios and increased confinement compared to T cells in lymph nodes and villi. The combination of these differences in motility patterns led to a decrease in the total volume scanned by T cells in lung compared to T cells in lymph node and villi. These results suggest that the tissue environment in which T cells move can impact the type of motility and ultimately, the efficiency of T cell search for target cells within specialized tissues such as the lung.