Final steps of natural killer cell maturation: a model for type 1-type 2 differentiation?
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.
Loza
M J
MJ
Kimmel Cancer Center, Jefferson Medical College, Department of Microbiology and Immunology, Philadelphia, PA, USA.
Perussia
B
B
D000943:Antigens, Differentiation / Q000032:analysis; D002454:Cell Differentiation; D002478:Cells, Cultured; D002999:Clone Cells; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018793:Interleukin-13 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000145:classification; D018448:Models, Immunological; D011971:Receptors, Immunologic / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D000943:Antigens, Differentiation; D018793:Interleukin-13; D011971:Receptors, Immunologic; D007371:Interferon-gamma