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
Cell Reports | CELL PRESS | Published : 2019
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. Gene..View full abstract
Awarded by NHMRC of Australia
The authors acknowledge the facilities, and scientific and technical assistance of Mr. Steve Cody at Monash Micro Imaging and members of the AMREP Flow Cytometry Core Facility at Monash University. We also acknowledge Dr. Rachael Borg, Dr. Evelyn Tsantikos, Dr. Jie-Yu Chung, Dr. Zeyad Nasa, Professor Magdalena Plebanski, Dr. Jennifer Boer, and Volga Tarlac for their assistance with experiments and for technical assistance. We acknowledge Professor Fabienne Mackay for supplying the mu-MT mice, Dr. Linda Wakim for the design of the antibody depletion experiment, Professor Joseph Trapani and Dr. Vivien Sutton (Peter MacCallum Cancer Centre) for help with the GrB and FasL analyses, and Dr. Nigel Jones and Dr. Bridgette Semple for assistance with the Morris water maze procedure. This study was supported by grants (APP1045755 and APP1126636) and a Fellowship (APP1044152) awarded to R.L.M. by the NHMRC of Australia, and by a Monash University, Faculty of Medicine, Nursing, and Health Sciences, Early Career Strategic Grant awarded to M.S.