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

Kyung Hwan Kim, Hee Tae Yu, Ilwoong Hwang, Sungha Park, Su Hyung Park, Sungjin Kim, Eui Cheol Shin

Research output: Contribution to journalArticle

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 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+, FcεRIγNKG2C+, and FcεRIγNKG2C NK cell populations were only evident after HCMV infection, but each had distinct characteristics. Among the subpopulations, FcεRIγNKG2C+ NK cells exhibited the most restricted killer immunoglobulin-like receptor repertoire, suggesting clonal expansion. Moreover, FcεRIγNKG2C+ NK cells exhibited the lowest Ki-67 and highest Bcl-2 expression, indicating the long-lived quiescent memory-like property. Functionally, FcεRIγNKG2C+ 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+, FcεRIγNKG2C+, and FcεRIγNKG2C 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.

Original languageEnglish (US)
Article number2865
JournalFrontiers in immunology
Volume10
DOIs
StatePublished - Dec 6 2019

Keywords

  • cytomegalovirus
  • FcεRIγ
  • human
  • memory
  • NK cell
  • NKG2C

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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