T cells contribute to the pathophysiology of ischemic stroke by yet unknown mechanisms. Mice with transgenic T cell receptors (TCR) and mutations in co-stimulatory molecules were used to define the minimal immunological requirements for T cell-mediated ischemic brain damage. Stroke was induced in recombination activating gene 1-deficient (RAG1-/-) mice devoid of T and B cells, RAG1-/- mice reconstituted with B cells or T cells, TCR-transgenic mice bearing one single CD8+ (2C/RAG2, OTI/RAG1 mice) or CD4+ (OTII/RAG1, 2D2/RAG1 mice) TCR, mice lacking accessory molecules of TCR stimulation (CD28-/-, PD1-/-, B7-H1-/- mice) or mice deficient in non-classical T cells (NKT and γδ T cells) by transient middle cerebral artery occlusion (tMCAO). Stroke outcome was assessed at day 1. RAG1-/- mice and RAG1-/- mice reconstituted with B cells developed significantly smaller brain infarctions compared to controls but thrombus formation after FeCl3-induced vessel injury was unimpaired. In contrast, TCR-transgenic mice and mice lacking co-stimulatory TCR signals were fully susceptible to tMCAO similar to mice lacking NKT and γδ T cells. These findings were corroborated by adoptive transfer experiments. Our data demonstrate that T cells critically contribute to cerebral ischemia but their detrimental effect neither depends on antigen recognition nor TCR co-stimulation or thrombus formation.

  • Submitted October 14, 2009.
  • Accepted February 14, 2010.