T lymphocyte trafficking: a novel target for neuroprotection in traumatic brain injury.
Infiltration of T lymphocytes is a key feature in transplant rejection and in several autoimmune disorders, but the role of T lymphocytes in traumatic brain injury (TBI) is largely unknown. Here we studied trafficking of immune cells in the brain after experimental TBI. We found that scavenging of reactive oxygen species (ROS) at the endothelial level dramatically reduced the infiltration of activated T lymphocytes. Immune cell infiltration was studied 12 h to 7 days after controlled cortical contusion in rats by ex vivo propagation of T lymphocytes (TcR+, CD8+), neutrophils (MPO+), and macrophages/microglia (ED-1+) from biopsies taken from injured cortex and analyzed by flow cytometry, as well as by quantitative immunohistochemistry. T lymphocyte and neutrophil infiltration peaked at 24 h and macrophages/microglia at 7 days post-injury. Pretreatment with 2-sulfophenyl-N-tert-butyl nitrone (S-PBN) produced a dramatic reduction of TcR+ T lymphocytes and a significantly smaller attenuation of neutrophil infiltration at 24 h post-injury, but did not affect CD8+ T lymphocytes or macrophages/microglia. S-PBN significantly reduced the expression of the endothelial adhesion molecules ICAM-1 and VCAM at 24 h for following TBI. We conclude that ROS inhibition at the endothelial level influenced T lymphocyte and neutrophil infiltration following TBI. We submit that the reduction of T lymphocyte infiltration is a key feature in improving TBI outcome after S-PBN treatment. Our data suggest that targeting T lymphocyte trafficking to the injured brain at the microvascular level is a novel concept of neuroprotection in TBI and warrants further exploration.
Clausen
Fredrik
F
Department of Neuroscience, Section of Neurosurgery, Uppsala University Hospital, Uppsala, Sweden.
Lorant
Tomas
T
Lewén
Anders
A
Hillered
Lars
L
D000818:Animals; D001557:Benzenesulfonates / Q000494:pharmacology*; D001930:Brain Injuries / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000502:physiology; D020556:Neutrophil Infiltration / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D001557:Benzenesulfonates; D019010:Vascular Cell Adhesion Molecule-1; C094272:N-tert-butyl-(2-sulfophenyl)nitrone; D018799:Intercellular Adhesion Molecule-1