| First Author | Daglas M | Year | 2019 |
| Journal | Cell Rep | Volume | 29 |
| Issue | 5 | Pages | 1178-1191.e6 |
| PubMed ID | 31665632 | Mgi Jnum | J:300773 |
| Mgi Id | MGI:6488906 | Doi | 10.1016/j.celrep.2019.09.046 |
| Citation | Daglas M, et al. (2019) Activated CD8(+) T Cells Cause Long-Term Neurological Impairment after Traumatic Brain Injury in Mice. Cell Rep 29(5):1178-1191.e6 |
| abstractText | 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. |
