Aging blood factors promote CD8+ T cell infiltration in the adult mouse brain

Abstract Aging coincides with major changes in brain immunity that aid in a decline in neuronal function. Here, we postulate that systemic, pro-aging factors contribute to immunological changes that occur within the brain during aging. To investigate this hypothesis, we first characterized the immune landscape upon aging in 20-month-old mice using cytometry by time-of-flight (CyTOF) and observed that memory T cells expanded in the circulation and that specifically effector CD8+ T cells expressing programmed cell death protein 1 (PD-1) and tissue-resident memory CD8+ T cells accumulated in the aged brain. Injections of plasma derived from 20-month-old mice into 5-month-old receiving mice decreased the frequency of splenic and circulating naïve T cells, increased memory CD8+ T cells and non-classical, patrolling monocytes in the spleen, and elevated levels of regulatory T cells and non-classical monocytes in the blood. Finally, we found an accumulation of CD8+ T cells within the brain parenchyma of plasma-treated mice, which coincided with expression of vascular cell adhesion molecule 1 (VCAM-1), a mediator of immune cell trafficking, on the brain vasculature and increased numbers of proliferating microglia. Taken together, our data highlight a role for CD8+ T cells in the aged brain and suggests involvement of age-associated systemic factors that mediate CD8+ T cell migration and expansion in the brain parenchyma.