Impaired development of adaptive NK cells during chronic CMV infection in aging populations

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B579
Abstract ID: 7634

Presenting Author:
Tao Peng , Assistant Investigator at Allen Inst. for Immunol.

Abstract:

Although substantial literatures demonstrate significant changes of CD8 T cells during aging and CMV infection, much less is known on how these two factors regulate innate cell types such as NK cells in humans. We have generated and analyzed single cell RNA-seq (sc-RNA-seq) data of PBMC from 107 subjects with three distinct age groups (pediatric (10-12 years old), young adults (25-35) and older adults (55-65)). CMV seropositive rates within the three age groups go up from 28% to 38% to 55%. Analysis of this large scRNA-seq dataset shows significant reprogramming of NK cells during aging and/or CMV infection. Although NK frequency in total PBMC is not significantly different among the age groups, adaptive NK cell frequency in total NK cells is significantly reduced in CMV⁺ older adults as compared to such cells in CMV⁺ younger groups; adaptive NK cell frequency is stable within one-year period in the three age groups; adaptive NK cells in CMV⁺ older adults have significantly reduced expression of KLRC2 and GZMH, and significantly up-regulated expression of ZBTB16 (encoding PLZF) as compared to such cells from CMV⁺ younger groups. Down-regulation of PLZF is known to mediate NK cell differentiation to adaptive NK cells. In summary, these studies suggest that development of adaptive NK cells is impaired in older CMV⁺ individuals as compared to CMV⁺ younger groups. Adaptive NK cells could be engineered to control CMV infection in immune compromised patients.