Abstract 4147496: Lack of CD8 T Cells impacts cerebral perfusion and cognitive function without altering cerebral vascular reactivity

It is well known the role of CD8 T cells in the onset hypertension and associated injury. We and others have recently shown the role of CD8 in hypertensive cerebral vascular damage, mediated by the secretion of interferon gamma leading to capillary rarefaction in both cortex and white matter and loss of cognitive functions. Thus, our aim was to explore whether CD8 can exert a physiological role in the cerebral vasculature in absence of any cardiovascular challenge. We assessed advanced neuroimaging and behavioural phenotyping in mice lacking CD8 T cells (CD8 KO) and matched wildtype controls (CD8 WT). We performed perfusion imaging of the brain by 7T MRI to evaluate the cerebral blood flow, Morris water maze (MWM) test and Novel Object Recognition (NOR) to evaluate learning and memory function. The reactivity of the middle cerebral artery (MCA) was also analyzed by pressure myography. CD8 KO showed a slight but significant hypoperfusion in the cerebral cortex (Figure A, ANOVA F on genotype effect F=13.58, p=0.0042), paired with a slower learning capability shown at MWM (Figure B, ANOVA F on genotype effect F=8.561, p=0.0104), and worse recognition capabilities at NOR (Figure C, t=2.537, p=0.0442). To understand whether the impact of CD8 cells on CBF was associated with abnormal cerebral vascular tone we evaluated MCA myogenic tone, evidencing no differences between CD8 WT and KO mice (Figure D). Our results shown that the presence of CD8 T cells is crucial for an adequate cerebral perfusion and such a condition realizes a cognitive dysfunction. This phenotype is independent of any cardiovascular challenge and of alteration of cerebral myogenic tone.