Reviews and feature articleTH2 heterogeneity: Does function follow form?

TH2 immune responses are required for the 2 fundamental pathological processes characteristic of allergic disease: IgE-mediated hypersensitivity and eosinophilic inflammation. The 3 established TH2 cytokines, IL-4, IL-5, and IL-13, each play a nonredundant role in allergic disease pathology. The recent explosion of TH subpopulations combined with the wide availability of polychromatic cytokine staining has facilitated the discovery of TH2 lineage heterogeneity. In this article we review TH2 heterogeneity and ask the following question: At what point do these subpopulations graduate from in vitro curiosities to immunologically robust therapeutic targets? We propose criteria to establish a T-cell subset as a biologically relevant entity and address the evidence to support these TH2 subpopulations having a unique function or specific contribution to allergic pathology or host defense.