Differentiation of NK1 and NK2 cells

Natural killer type-1 (NK1)/NK2 terminology was proposed as an analogy to T helper type-1 (Th1)/Th2 subsets of CD4 T cells. In addition to well recognized IFN-gamma-producing NK1 cells, recent accumulating evidence suggests the presence and the regulatory function of NK2 cells, which produce type-2 cytokines, such as IL-5 and IL-13. Most studies on the production of cytokines by NK1/NK2 subsets have been performed in the human system. Recently, a mouse in vitro NK1/NK2 cell differentiation system was established. A linear 2-0-1 model has been proposed for the differentiation of NK1/NK2 cell subsets, but the branching NK1/NK2 cell differentiation model, comparable to Thl/Th2 cell differentiation, remains a likely explanation. In this review, we summarize the evidence indicating the unique features of NK1/NK2 cells and discuss the above two NK cell differentiation models. In addition, we point to interesting similarities in the expression of transcription factors that regulate cytokine production in NK cells and CD8 T cells.