Human Cytomegalovirus Infection Promotes Expansion of a Functionally Superior Cytoplasmic CD3⁺ NK Cell Subset with a Bcl11b-Regulated T Cell Signature.

ABSTRACT: Human CMV (HCMV) is a ubiquitous pathogen that indelibly shapes the NK cell repertoire. Using transcriptomic, epigenomic, and proteomic approaches to evaluate peripheral blood NK cells from healthy human volunteers, we find that prior HCMV infection promotes NK cells with a T cell-like gene profile, including the canonical markers CD3ε, CD5, and CD8β, as well as the T cell lineage-commitment transcription factor Bcl11b. Although Bcl11b expression is upregulated during NK maturation from CD56^bright to CD56^dim, we find a Bcl11b-mediated signature at the protein level for FcεRIγ, PLZF, IL-2Rβ, CD3γ, CD3δ, and CD3ε in later-stage, HCMV-induced NK cells. BCL11B is targeted by Notch signaling in T cell development, and culture of NK cells with Notch ligand increases

SUBMITTER: Wu Z 

PROVIDER: S-EPMC8578400 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature