Generalized Lévy walks and the role of chemokines in migration of effector CD8+ T cells

Abstract

Chemokines play a central role in regulating processes essential to the immune function of T cells1-3, such as their migration within lymphoid tissues and targeting of pathogens in sites of inflammation. Here we track T cells using multi-photon microscopy to demonstrate that the chemokine CXCL10 enhances the ability of CD8+ T cells to control the pathogen T. gondii in the brains of chronically infected mice. This chemokine boosts T cell function in two different ways: it maintains the effector T cell population in the brain and speeds up the average migration speed without changing the nature of the walk statistics. Remarkably, these statistics are not Brownian; rather, CD8+ T cell motility in the brain is well described by a generalized Lévy walk. According to our model, this surprising feature enables T cells to find rare targets with more than an order of magnitude more efficiency than Brownian random walkers. Thus, CD8+ T cell behavior is similar to Lévy strategies reported in organisms ranging from mussels to marine predators and monkeys4-10, and CXCL10 aids T cells in shortening the average time to find rare targets.

In vivo imaging of CD8+T cell-mediated elimination of malaria liver stages

“…A recent study has reported that Toxoplasma-specific effector CD8 + T cells adopt a generalized Lévy random walk, which optimizes their ability to find rare infected cells in the brain (26). It will be interesting to determine whether a similar process is happening with Plasmodium-specific cells in the liver.…”

Slow Lévy flights

“…Power-law distributions of step lengths with diverging variance, a key feature of Lévy processes, are found to describe well the trajectories of immune cells in the brain [11], the displacements of animals [12][13][14][15] and hunter-gatherers [16,17] in their environments, or the travels of modern humans within and between cities [18][19][20][21]. However, the assumption of independence between steps does limit the applicability of genuine Lévy processes for modeling real systems, where non-Markovian effects and correlations can be strong.…”

Emergence of Lévy walks in systems of interacting individuals

“…Lévy walk [1][2][3] is an important concept which describes a wide spectrum of physical and biological processes involving stochastic transport [4][5][6][7][8][9][10]. Cold atoms moving in dissipative optical lattices [11], endosomal active transport in living cells [12], and T-cells migrating in the brain tissue [13] are just several examples where Lévy walks were reported. It is argued that living organisms can use Lévy transport to accelerate pattern formation [14] and to optimize searching for sparse food [15][16][17][18].…”