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Cell Rep. 2019 Oct 29;29(5):1178-1191.e6. doi: 10.1016/j.celrep.2019.09.046.

Activated CD8+ T Cells Cause Long-Term Neurological Impairment after Traumatic Brain Injury in Mice.

Author information

1
Molecular Neurotrauma and Haemostasis, Australian Centre for Blood Diseases, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia.
2
Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia.
3
Molecular Neurotrauma and Haemostasis, Australian Centre for Blood Diseases, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia. Electronic address: maithili.sashindranath@monash.edu.
4
Molecular Neurotrauma and Haemostasis, Australian Centre for Blood Diseases, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia. Electronic address: robert.medcalf@monash.edu.

Abstract

Traumatic brain injury (TBI) leaves many survivors with long-term disabilities. A prolonged immune response in the brain may cause neurodegeneration, resulting in chronic neurological disturbances. In this study, using a TBI mouse model, we correlate changes in the local immune response with neurodegeneration/neurological dysfunction over an 8-month period. Flow cytometric analysis reveals a protracted increase in effector/memory CD8+ T cells (expressing granzyme B) in the injured brain. This precedes interleukin-17+CD4+ T cell infiltration and is associated with progressive neurological/motor impairment, increased circulating brain-specific autoantibodies, and myelin-related pathology. Genetic deficiency or pharmacological depletion of CD8+ T cells, but not depletion of CD4+ T cells, improves neurological outcomes and produces a neuroprotective Th2/Th17 immunological shift, indicating a persistent detrimental role for cytotoxic T cells post-TBI. B cell deficiency results in severe neurological dysfunction and a heightened immune reaction. Targeting these adaptive immune cells offers a promising approach to improve recovery following TBI.

KEYWORDS:

B cells; CD8(+) T cells; adaptive immune cells; autoantibodies; granzyme B; neuroimmunology; traumatic brain injury

PMID:
31665632
DOI:
10.1016/j.celrep.2019.09.046
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