Neuroprotection against ischemic stroke requires a specific class of early responder T cells in mice

J Clin Invest. 2022 Aug 1;132(15):e157678. doi: 10.1172/JCI157678.


Immunomodulation holds therapeutic promise against brain injuries, but leveraging this approach requires a precise understanding of mechanisms. We report that CD8+CD122+CD49dlo T regulatory-like cells (CD8+ TRLs) are among the earliest lymphocytes to infiltrate mouse brains after ischemic stroke and temper inflammation; they also confer neuroprotection. TRL depletion worsened stroke outcomes, an effect reversed by CD8+ TRL reconstitution. The CXCR3/CXCL10 axis served as the brain-homing mechanism for CD8+ TRLs. Upon brain entry, CD8+ TRLs were reprogrammed to upregulate leukemia inhibitory factor (LIF) receptor, epidermal growth factor-like transforming growth factor (ETGF), and interleukin 10 (IL-10). LIF/LIF receptor interactions induced ETGF and IL-10 production in CD8+ TRLs. While IL-10 induction was important for the antiinflammatory effects of CD8+ TRLs, ETGF provided direct neuroprotection. Poststroke intravenous transfer of CD8+ TRLs reduced infarction, promoting long-term neurological recovery in young males or aged mice of both sexes. Thus, these unique CD8+ TRLs serve as early responders to rally defenses against stroke, offering fresh perspectives for clinical translation.

Keywords: Immunotherapy; Inflammation; Neuroscience; Stroke; T cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / metabolism
  • Female
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Ischemic Stroke*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neuroprotection
  • Stroke* / genetics
  • Stroke* / metabolism


  • Interleukin-10