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

Analysis of cytokine and differentiation antigen expression in human natura l killer (NK) cells revealed that interleukin 13 (IL-13) and interferon gam ma (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-independ ent accumulation of IFN-gamma (+) cells. These data disproved the NK1-NK2 h ypothesis and challenge the current T helper 1 (THI)-T(H)2 paradigm. We pro pose that the cytokine environment regulates a type 2 -->0 -->1 development al progression, with IL-12 needed for terminal differentiation and IL-4 del aying this process, rather than a type 1 versus type 2 decision of a type 0 cell.