Generation of human natural killer cells from immature progenitors does not require marrow stromal cells

Maria R.G. Silva, Ronald Hoffman, Edward F. Srour, Joao L. Ascensao

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Human natural killer (NK) cells comprise 10% to 15% of peripheral blood mononuclear cells and have an important role in immune responses against tumors, viral infections, and graft rejection. NK cells originate in bone marrow (BM), but their progenitors and lineage development have not been completely characterized. We studied the generation of NK cells from purified CD34+HLADR- and CD34+HLADR+ BM progenitors and the influence of various cytokines on their production. We show that CD3-CD56+ cytotoxic NK cells can develop from both progenitor populations when interleukin-2 (IL-2) is present in an in vitro suspension culture system containing IL-1α and stem cell factor. Up to 83.8% and 98.6% CD3 CD56+ cells were detected in CD34+HLADR- and CD34+DR+ cultures, respectively, after 5 weeks of culture; significant numbers of NK cells were first detected after 2 weeks. Cytotoxic activity paralleled NK cell numbers; up to 70% specific lysis at an effector:target ratio of 10:1 was observed at 5 weeks. IL-7 also triggered development of CD3-CD56+ cells from these immature progenitors (up to 24% and 55% appeared in CD34+HLADR- and CD34+HLADR+ cultures, respectively). Our data suggest that BM stromas are not necessary for NK cell development and that IL-2 remains essential for this lineage development and differentiation.

Original languageEnglish (US)
Pages (from-to)841-846
Number of pages6
JournalBlood
Volume84
Issue number3
StatePublished - Aug 1 1994
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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