Dataset Information

Phenotypic and Functional Analysis of Human NK Cell Subpopulations According to the Expression of FcεRIγ and NKG2C.

ABSTRACT: Human memory-like NK cells are commonly defined by either a lack of FcεRIγ or gain of NKG2C expression. Here, we investigated the heterogeneity of human CD56^dim NK cell subpopulations according to the expression of FcεRIγ and NKG2C in a large cohort (n = 127). Although the frequency of FcεRIγ^- and NKG2C⁺ NK cells positively correlated, the FcεRIγ^- and NKG2C⁺ NK cell populations did not exactly overlap. The FcεRIγ⁺NKG2C⁺, FcεRIγ^-NKG2C⁺, and FcεRIγ^-NKG2C^- NK cell populations were only evident after HCMV infection, but each had distinct characteristics. Among the subpopulations, FcεRIγ^-NKG2C⁺ NK cells exhibited the most restricted killer immunoglobulin-like receptor repertoire, suggesting clonal expansion. Moreover, FcεRIγ^-NKG2C⁺ NK cells exhibited the lowest Ki-67 and highest Bcl-2 expression, indicating the long-lived quiescent memory-like property. Functionally, FcεRIγ^-NKG2C⁺ NK cells had weak natural effector function against K562 but strong effector functions by CD16 engagement, whereas FcεRIγ⁺NKG2C⁺ NK cells had strong effector functions in both settings. Anatomically, the FcεRIγ⁺NKG2C⁺, FcεRIγ^-NKG2C⁺, and FcεRIγ^-NKG2C^- NK cell populations were present in multiple human peripheral organs. In conclusion, we demonstrate the heterogeneity of memory-like NK cells stratified by FcεRIγ and NKG2C and suggest both markers be utilized to better define these cells.

SUBMITTER: Kim KH

PROVIDER: S-EPMC6908468 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Phenotypic and Functional Analysis of Human NK Cell Subpopulations According to the Expression of FcεRIγ and NKG2C.

Kim Kyung Hwan KH Yu Hee Tae HT Hwang Ilwoong I Park Sungha S Park Su-Hyung SH Kim Sungjin S Shin Eui-Cheol EC

Frontiers in immunology 20191206

Human memory-like NK cells are commonly defined by either a lack of FcεRIγ or gain of NKG2C expression. Here, we investigated the heterogeneity of human CD56dim NK cell subpopulations according to the expression of FcεRIγ and NKG2C in a large cohort (n = 127). Although the frequency of FcεRIγ- and NKG2C+ NK cells positively correlated, the FcεRIγ- and NKG2C+ NK cell populations did not exactly overlap. The FcεRIγ+NKG2C ...[more]

PMID: 31867015

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Project description:BackgroundInfections with the Puumala orthohantavirus (PUUV) in humans may cause hemorrhagic fever with renal syndrome (HFRS), known as nephropathia epidemica (NE), which is associated with acute renal failure in severe cases. In response to PUUV-infections, a subset of potent antiviral NKG2C+ NK cells expand, whose role in virus defence and pathogenesis of NE is unclear. NKG2C+ NK cell proliferation is mediated by binding of NKG2C/CD94 to HLA-E on infected cells. The proliferation and activation of NKG2C+ NK cells via the NKG2C/HLA-E axis is affected by different NKG2C (NKG2Cwt/del) and HLA-E (HLA-E*0101/0103) alleles, which naturally occur in the human host. Homozygous (NKG2Cdel/del) and heterozygous (NKG2Cwt/del) deletions of the NKG2C receptor results in an impaired NKG2C/CD94 mediated proliferation and activation of NKG2C+ cells. We therefore analyzed the PUUV-mediated NKG2C+ NK cell responses and the impact of different NKG2C and HLA-E alleles in NE patients.Methodology/principal findingsNKG2C+ NK cell expansion and effector functions in PUUV-infected cells were investigated using flow cytometry and it was shown that PUUV-infected endothelial cells led to a NKG2C/CD94 mediated NKG2C+ NK cell activation and expansion, dependent on the HLA-G-mediated upregulation of HLA-E. Furthermore, the NKG2Cdel and HLA-E*0101/0103 alleles were determined in 130 NE patients and 130 matched controls, and it was shown that in NE patients the NKG2Cwt/del allele was significantly overrepresented, compared to the NKG2Cwt/wt variant (p = 0.01). In addition, in vitro analysis revealed that NKG2Cwt/del NK cells exhibited on overall a lower proliferation (p = 0.002) and lower IFNγ expression (p = 0.004) than NKG2Cwt/wt NK cells.Conclusions/significanceOur results corroborate the substantial impact of the NKG2C/HLA-E axis on PUUV-specific NK cell responses. A weak NKG2C+ NK cell response, as reflected by NKG2Cwt/del variant, may be associated with a higher risk for a severe hantavirus infections.

Dataset Information

Phenotypic and Functional Analysis of Human NK Cell Subpopulations According to the Expression of FcεRIγ and NKG2C.

Publications

Phenotypic and Functional Analysis of Human NK Cell Subpopulations According to the Expression of FcεRIγ and NKG2C.

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