期刊
AGING-US
卷 11, 期 2, 页码 724-740出版社
IMPACT JOURNALS LLC
DOI: 10.18632/aging.101774
关键词
aging; CMV; EBV; CD56-negative; NK cells; senescence; exhaustion
资金
- Swiss National Foundation [P300PB_ 161092, P2BSP3_ 151877, 31003A_172848]
- British Biotechnology and Biological Science Research Council [BB/L005328/1]
- BBSRC [BB/L005328/1] Funding Source: UKRI
- Swiss National Science Foundation (SNF) [P300PB_161092, 31003A_172848, P2BSP3_151877] Funding Source: Swiss National Science Foundation (SNF)
Natural killer cells lacking expression of CD56 (CD56(neg) NK cells) have been described in chronic HIV and hepatitis C virus infection. Features and functions of CD56(neg) NK cells in the context of latent infection with CMV and/or EBV with age are not known. In a cohort of healthy donors >60 years of age, we found that co-infection with CMV and EBV drives expansion of CD56(neg) NK cells. Functionally, CD56(neg) NK cells displayed reduced cytotoxic capacity and IFN-gamma production, a feature that was enhanced with CMV/EBV co-infection. Further, the frequency of CD56(neg) NK cells correlated with accumulation of end-stage-differentiated T cells and a reduced CD4/CD8 T cell ratio, reflecting an immune risk profile. CD56(neg) NK cells had a mature phenotype characterized by low CD57 and KIR expression and lacked characteristics of cell senescence. No changes in their activating NK cell receptor expression, and no upregulation of the negative co-stimulation receptors PD-1 or TIM-3 were observed. In all, our data identify expansion of dysfunctional CD56(neg) NK cells in CMV+EBV+ elderly individuals suggesting that these cells may function as shape-shifters of cellular immunity and argue for a previously unrecognized role of EBV in mediating immune risk in the elderly.
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