Do functional subsets of leukocytes arise by divergent or linear differentiation?

Summary The T helper type 1 (Th1)/Th2 paradigm has been extended to a wide variety of leukocyte lineages since its inception, including innate immune cells such as dendritic cells and natural killer (NK) cells. Recently, studies of human NK cells have led to the proposition of a new model of linear differentiation in which cell phenotype is controlled by regulation of proliferation versus differentiation, rather than by divergent differentiation programmes. It was suggested that this model might also apply to T cells. Here we discuss the relevance of each model to different leukocyte lineages and argue that the linear differentiation model does not apply to αβ T cells.