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

Abstract

T cells in the brains of Toxoplasma-infected mice are shown to move by Lévy-like walks. T cells are an important first point of contact between the immune system and invading pathogens. The currently accepted model of the early stages of the immune reaction, in which the T cells encounter the invader, is that of a Brownian random walk. This paper reports the use of in vivo multiphoton microscopy to demonstrate that the chemokine CXCL10 enhances the ability of CD8+ T cells to control the protozoon pathogen Toxoplasma gondii. Surprisingly, the in vivo imaging reveals that T cells in the brains of mice infected with T. gondii move not by Brownian-type motion but instead follow a Lévy walk pattern of runs punctuated by periodic pauses. Mathematical simulations suggest that this mode of movement increases the chances of finding targets at unknown locations. Chemokines have a central role in regulating processes essential to the immune function of T cells1,2,3, 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 Toxoplasma 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. Notably, 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 unexpected 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 behaviour is similar to Lévy strategies reported in organisms ranging from mussels to marine predators and monkeys4,5,6,7,8,9,10, and CXCL10 aids T cells in shortening the average time taken to find rare targets.