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How and why do T cells and their derived cytokines affect the injured and healthy brain?

Abstract

The evolution of adaptive immunity provides enhanced defence against specific pathogens, as well as homeostatic immune surveillance of all tissues. Despite being 'immune privileged', the CNS uses the assistance of the immune system in physiological and pathological states. In this Opinion article, we discuss the influence of adaptive immunity on recovery after CNS injury and on cognitive and social brain function. We further extend a hypothesis that the pro-social effects of interferon-regulated genes were initially exploited by pathogens to increase host–host transmission, and that these genes were later recycled by the host to form part of an immune defence programme. In this way, the evolution of adaptive immunity may reflect a host–pathogen 'arms race'.

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Figure 1: Immune cells reside in meningeal spaces.
Figure 2: A summary of T cell activity in the injured CNS.
Figure 3: IFNγ is necessary for social behaviour.
Figure 4: Proposed mechanisms for the role of IFNγ in a hypothesized evolutionary 'arms race'.

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Acknowledgements

The authors thank S. Smith for editing the manuscript and A. Impagliazzo for helping with the artwork. The authors also thank all the members of the Kipnis laboratory for their insightful comments and enlightening ideas. This work was supported by grants from the US National Institutes of Health (AG034113, NS096967 and MH108156 to J.K., and T32-AI007496 to A.J.F.) and the Hartwell Foundation (to A.J.F.).

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Correspondence to Anthony J. Filiano or Jonathan Kipnis.

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Filiano, A., Gadani, S. & Kipnis, J. How and why do T cells and their derived cytokines affect the injured and healthy brain?. Nat Rev Neurosci 18, 375–384 (2017). https://doi.org/10.1038/nrn.2017.39

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