Brain-localized CD4 and CD8 T cells perform correlated random walks and not Levy walks

Abstract

Background. For survival of the organism, T cells must efficiently control pathogens invading different peripheral tissues. Whether or not such control is achieved by utilizing different movement strategies in different tissues remains poorly understood. Liver-localized CD8 T cells perform correlated random walks  --- a type of a Brownian walk -- in liver sinusoids but in some condition these T cells may also perform Levy flights -- rapid and large displacements by floating with the blood flow. CD8 T cells in lymph nodes or skin also undergo Brownian walks. A recent study suggested that brain-localized CD8 T cells, specific to Toxoplasma gondii, perform generalized Levy walks -- a walk type in which T cells alternate pausing and displacing long distances --- which may indicate that brain is a unique organ where T cells exhibit movement strategies different from other tissues. Methods.  We quantified movement patterns of brain-localized Plasmodium berghei-specific CD4 and CD8 T cells by using well-established statistical and computational methods. Results.  We found that T cells change their movement pattern with time since infection and that CD4 T cells move faster and turn less than CD8 T cells. Importantly, both CD4 and CD8 T cells move in the brain by correlated random walks without long displacements challenging previous observations. We have also re-analyzed the movement data of brain-localized CD8 T cells in T. gondii-infected mice and found no evidence of Levy walks. We hypothesize that the previous conclusion of Levy walks of T. gondii-specific CD8 T cells in the brain was reached due to missing time-frames in the data that create an impression of large movement lengths between assumed-to-be-sequential movements.  Conclusion. Our results suggests that movement strategies of CD8 T cells are largely similar between LNs, liver, and the brain and consistent with correlated random walks and not Levy walks.