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

Maria Daglas; Dominik F. Draxler; Heidi Ho; Fiona McCutcheon; Adam Galle; Amanda E. Au; Pia Larsson; Julia Gregory; Frank Alderuccio; Maithili Sashindranath; Robert L. Medcalf

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

2019

Summary: 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. : Daglas et al. show that granzyme B+CD8+ T cells accumulate in the brain after traumatic brain injury, triggering chronic neurological/motor impairment and myelin pathology. Genetic deficiency/pharmacological depletion of CD8+ T cells, but not B cells, promotes recovery post-injury and offers a therapeutic option to minimize long-term disabilities in trauma patients. Keywords: traumatic brain injury, CD8+ T cells, adaptive immune cells, B cells, autoantibodies, neuroimmunology, granzyme B

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