Final steps of natural killer cell maturation: a model for type 1-type 2 differentiation?

Nat Immunol. 2001 Oct;2(10):917-24. doi: 10.1038/ni1001-917.


Analysis of cytokine and differentiation antigen expression in human natural killer (NK) cells revealed that interleukin 13 (IL-13) and interferon gamma (IFN-gamma) are produced at sequential stages during irreversible IL-12-induced differentiation. In human NK cell clones, polyclonal CD3-CD161+CD56- cells and peripheral lymphocytes, IL-4 induced the proliferation of both IL-13+ NK and T cells, whereas IL-12 allowed a proliferation-independent accumulation of IFN-gamma+ cells. These data disproved the NK1-NK2 hypothesis and challenge the current T helper 1 (TH1)-TH2 paradigm. We propose that the cytokine environment regulates a type 2-->0-->1 developmental progression, with IL-12 needed for terminal differentiation and IL-4 delaying this process, rather than a type 1 versus type 2 decision of a type 0 cell.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, Differentiation / analysis
  • Cell Differentiation
  • Cells, Cultured
  • Clone Cells
  • Cytotoxicity Tests, Immunologic
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukin-13 / biosynthesis
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation
  • Lymphocyte Subsets / classification
  • Models, Immunological*
  • Receptors, Immunologic / metabolism
  • Th1 Cells / immunology*
  • Th2 Cells / immunology*


  • Antigens, Differentiation
  • Interleukin-13
  • Receptors, Immunologic
  • Interferon-gamma