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 but whether such control (and lack of thereof) is achieved by utilizing different movement strategies remains poorly understood. Liver-localized CD8 T cells perform correlated random walks (CRWs)— a type of a Brownian walk – in liver sinusoids but in some conditions, 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 (LWs) – 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 CRWs without long displacements challenging previous observations. We have also re-analyzed movement data of brain-localized CD8 T cells in T. gondii-infected mice from a previous study and found no evidence of LWs. We hypothesize that the previous conclusion of LWs of T. gondii-specific CD8 T cells in the brain was reached due to missing timeframes in the data that create an impression of large displacements between assumed-to-be sequential movements. Conclusion. Our results suggest that movement strategies of CD8 T cells are largely similar between LNs, liver, and the brain and consistent with CRWs and not LWs.