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

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

Maria Daglas¹, Dominik F Draxler¹, Heidi Ho¹, Fiona McCutcheon¹, Adam Galle¹, Amanda E Au¹, Pia Larsson¹, Julia Gregory¹, Frank Alderuccio², Maithili Sashindranath³, Robert L Medcalf⁴

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.

Presented By Maria Daglas | ORCID iD