IL-21 induces both rapid maturation of human CD34+ cell precursors towards NK cells and acquisition of surface killer Ig-like receptors

Simona Sivori, Claudia Cantoni, Silvia Parolini, Emanuela Marcenaro, Romana Conte, Lorenzo Moretta, Alessandro Moretta

Research output: Contribution to journalArticlepeer-review

Abstract

The NK cell maturation from CD34+ Lin- hematopoietic cell precursors is a complex process that requires the direct contact with stromal cells and/or the synergistic effect of different cytokines. In this study we show that IL-21 is capable of inducing an accelerated NK cell maturation when added to cultures of CD34+ Lin- cells isolated from human cord blood supplemented with IL-15, Flt3-L and SCF. After 25 days of culture, 50% of CD56+ cells expressed various NK cell markers including the NKp46 and NKp30 triggering receptors, the CD94/NKG2A inhibitory receptor and CD16. At day 35, substantial fractions of NK cells expressed KIR, CD8 and CD2, i.e. surface markers expressed by mature NK cells, that are virtually undetectable in developing NK cells cultured in the absence of IL-21. Remarkably, similar to mature NK cells all these markers were included in the CD56dim cell fraction, while the CD56bright population was only composed of CD94/NKG2A- and CD94/NKG2A+ cells. Thus, IL-21 allows the induction of a full NK cell maturation in vitro and offers an important tool for dissecting the molecular mechanisms involved in different steps of NK cell maturation and in the acquisition of a mature KIR repertoire.

Original languageEnglish
Pages (from-to)3439-3447
Number of pages9
JournalEuropean Journal of Immunology
Volume33
Issue number12
DOIs
Publication statusPublished - Dec 2003

Keywords

  • Killer Ig-like receptors
  • Lymphokines
  • Maturation
  • Natural killer cells precursors

ASJC Scopus subject areas

  • Immunology

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