| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
Cell Reports, Vol 29, Iss 5, Pp 1178-1191.e6 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2019.09.046 |
| Popis: |
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. : Daglas et al. show that granzyme B+CD8+ T cells accumulate in the brain after traumatic brain injury, triggering chronic neurological/motor impairment and myelin pathology. Genetic deficiency/pharmacological depletion of CD8+ T cells, but not B cells, promotes recovery post-injury and offers a therapeutic option to minimize long-term disabilities in trauma patients. Keywords: traumatic brain injury, CD8+ T cells, adaptive immune cells, B cells, autoantibodies, neuroimmunology, granzyme B |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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