Characterizing the movement strategy of CD8+ T cells in finding malaria parasites in the liver

Abstract

Abstract Movement strategies by which antigen-specific CD8+ T cells search for sites of infection in peripheral tissues are not fully understood. Measurable quantities, such as the distance traveled per unit of time, that follow Lévy statistics are common in nature, for example, in bacterial and higher animal foraging; in mussels, marine predators, monkeys. A recent study has shown that moving according to Lévy flights enables CD8+ T cells in the brain to find “rare targets” (Toxoplasma gondii-infected cells) in an order of magnitude more efficiently than using Brownian and other walking strategies. It has been, thus, suggested that such efficient strategy of T cell searching for infection may have been evolutionarily selected. However, T cells in the brain (or other tissues) are often constrained by the structure of the physical environment in which cells move. Whether the emerged statistical pattern of T cell movement is due to a cell-intrinsic program or a consequence of environmental constrains is, thus, unknown. Here, we address this question by using intravital imaging of movement of Plasmodium-specific CD8+ T cells in murine livers and mathematical modeling and analyses of the generated data. We investigate whether the physical structure of the movement paths in the liver plays a role in shaping the walking strategy of T cells in finding malaria parasites. Here, we map out liver sinusoids in 3D using intravital microscopy and use simulations to parameterize the alternative walking models by fitting them to empirical data having no references to the physical structure. Our preliminary data suggest that constraints imposed by the structure of liver sinusoids significantly impact the moving pattern of the T cells.