Liver-localized CD8 T cells do not need Levy walks to be efficient killers

Abstract

Abstract Pathogen-specific CD8 T cells face the problem of finding rare cells that present their cognate antigen either in the lymph node or infected tissue. To optimize the search for rare targets it has been proposed that T cells might perform a random walk with long displacements called Levy walks enabling superdiffusive behavior and shorter search times which may be evolutionary selected. We examined the behavior of activated CD8 T cells in the liver where both the movement of the cells and the underlying structural constraints can be clearly defined. We show that Plasmodium-specific liver-localized CD8 T cells perform short displacement, Brownian-like walks and yet display transiently superdiffusive displacement, the cardinal feature of efficient Levy walks. Because liver-localized CD8 T cells are mainly associated with liver sinusoids, simulations of Brownian or Levy walkers in structures derived from the liver sinusoids illustrate that structure together with preferred forward movement results in superdiffusive movement. Interestingly, Brownian walkers require less time to find a rare target when T cells search for the infection in physiologically-derived liver structures. Our results strongly suggest that observed patterns of movement of CD8 T cells are likely to result from a combination of a cell-intrinsic movement program, physical constraints imposed by the environmental structures, and other environmental cues. Future work needs to focus on quantifying the relative contributions of these factors to the overall observed movement patterns of biological agents.