Experimental ischemic stroke induces long-term T cell activation in the brain

J Cereb Blood Flow Metab. 2019 Nov;39(11):2268-2276. doi: 10.1177/0271678X18792372. Epub 2018 Aug 10.

Abstract

Mounting evidence has demonstrated that both innate and adaptive immune cells infiltrate into the brain after ischemic stroke. T cell invasion has been found in the ischemic region up to one month post experimental ischemic stroke and has been shown to persist for years in stroke patients. However, the function and phenotypic characteristics of the brain invading T cells after ischemic stroke have not been investigated. In the current study, we determined the function of brain invading T cells in the acute and chronic phase following experimental ischemic stroke induced by transient middle cerebral artery occlusion. We observed a significant increase of CD4+ and CD8+ T cells presented in the peri-infarct area at up to one month after experimental ischemic stroke. The brain invading T cells after ischemic stroke demonstrated close interaction with active astrocytes and a progressive proinflammatory phenotype as evidenced by the increased expression of T cell activation markers CD44 and CD25, proinflammatory cytokines INF-γ, IL-17, IL-10, TNF-α, and perforin, with corresponding transcriptional factors T-bet and RORc. Our results indicated a prolonged activation of brain invading CD4+ and CD8+ T cells after ischemic stroke which may play a role in the neural repair process after stroke.

Keywords: Immune; T lymphocyte; flow cytometry; ischemic stroke; middle cerebral artery occlusion.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain Ischemia / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology
  • Cell Movement
  • Cytokines / metabolism
  • Infarction, Middle Cerebral Artery
  • Lymphocyte Activation / immunology*
  • Mice
  • Stroke / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology
  • Time Factors
  • Transcription Factors / metabolism

Substances

  • Cytokines
  • Transcription Factors