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

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)1178-1191.e6
Number of pages20
JournalCell Reports
Volume29
Issue number5
DOIs
Publication statusPublished - 29 Oct 2019

Keywords

  • adaptive immune cells
  • autoantibodies
  • B cells
  • CD8 T cells
  • granzyme B
  • neuroimmunology
  • traumatic brain injury

Cite this

Daglas, Maria ; Draxler, Dominik F. ; Ho, Heidi ; McCutcheon, Fiona ; Galle, Adam ; Au, Amanda E. ; Larsson, Pia ; Gregory, Julia ; Alderuccio, Frank ; Sashindranath, Maithili ; Medcalf, Robert L. / Activated CD8+ T Cells Cause Long-Term Neurological Impairment after Traumatic Brain Injury in Mice. In: Cell Reports. 2019 ; Vol. 29, No. 5. pp. 1178-1191.e6.
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Activated CD8+ T Cells Cause Long-Term Neurological Impairment after Traumatic Brain Injury in Mice. / Daglas, Maria; Draxler, Dominik F.; Ho, Heidi; McCutcheon, Fiona; Galle, Adam; Au, Amanda E.; Larsson, Pia; Gregory, Julia; Alderuccio, Frank; Sashindranath, Maithili; Medcalf, Robert L.

In: Cell Reports, Vol. 29, No. 5, 29.10.2019, p. 1178-1191.e6.

Research output: Contribution to journalArticleResearchpeer-review

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