Neuroinflammation plays a key role in secondary @entity75 after @entity64 . Although deleterious effects of proinflammatory cytokines are well characterized, direct cytotoxic effects of invading immune cells on the @entity63 brain and the importance of their antigen-dependent activation are essentially unknown. Here we examined the effects of adaptive and innate immune cells-cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells-that share the direct perforin-mediated cytotoxic pathway on outcome after @entity2806 in @entity19 . Although CTLs and NK cells both invaded the @entity63 brain, only brain-infiltrating CTLs but not NK cells were more activated than their splenic counterparts. Depletion of CTLs decreased @entity1188 volumes and behavioral deficit in two @entity63 models, whereas NK cell depletion had no effect. Correspondingly, adoptive CTL transfer from wild-type into @entity5350 knock-out @entity19 increased @entity1188 size. Adoptive CTL transfer from perforin knock-out or interferon-y knock-out @entity19 into @entity5350 knock-out @entity19 revealed that CTL @entity2359 was mediated by perforin. Accordingly, CTLs isolated from wild-type or interferon-y knock-out but not from perforin knock-out @entity19 induced neuronal cell death in vitro. CTLs derived from ovalbumin-specific T-cell receptor @entity19 were not activated and infiltrated less into the @entity63 brain compared with wild-type CTLs. Their transfer did not increase the @entity1188 size of @entity5350 knock-out mice, indicating antigen-dependent activation as an essential component of CTL @entity2359 . Our findings underscore the importance of antigen-dependent, direct cytotoxic immune responses in @entity64 and suggest modulation of CTLs and their effector pathways as a potential new strategy for @entity64 therapy.

Antigen dependently activated cluster of differentiation 8-positive T cells cause perforin-mediated @entity2359 in experimental XXXX .

@entity64 :: ('MESH:D020521', 'Disease') :: ['stroke'] @entity2806 :: ('MESH:D002545', 'Disease') :: ['cerebral ischemia'] @entity63 :: ('MESH:D007511', 'Disease') :: ['ischemia', 'ischemic'] @entity75 :: ('MESH:D001927', 'Disease') :: ['brain damage'] @entity19 :: ('10090', 'Species') :: ['mice', 'transgenic mice'] @entity1188 :: ('MESH:D007238', 'Disease') :: ['infarct'] @entity5350 :: ('19373(Tax:10090)', 'Gene') :: ['Rag1'] @entity2359 :: ('MESH:D020258', 'Disease') :: ['neurotoxicity']
@entity64 :: (MESH:D020521,Disease) :: ['stroke']
