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

Highlights

• Granzyme B⁺ CD8⁺ T cells accumulate in the brain after traumatic brain injury (TBI)

• Brain CD8⁺ T cells contribute to chronic motor deficits and myelin pathology

• Deficiency/depletion of CD8⁺ T cells promotes neurological recovery following TBI

• B cells and autoreactive antibodies appear to play a regulatory role in TBI

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.