Understanding the roles of basophils: breaking dawn

Early studies that used parasite-infected interleukin-4 (IL-4) reporter animals led us to identify basophils as the primary source of IL-4 and hence propose the hypothesis that basophils trigger the development of antigen-specific T helper type 2 (Th2) immune responses in vivo. These findings appeared to resolve a long-standing puzzle underlying Th2 immunity, that is, what is the source of the initial IL-4 necessary for CD4 T-cell differentiation into Th2 effector cells?. However, results from extensive investigations of the contribution of basophils to Th2 immunity unveiled some controversial data that cast doubt on the initial hypothesis. In this review, the consensus and the controversy regarding the roles of basophils in infection and immunity, as well as outstanding questions for the future, are discussed.