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Helper T cell heterogeneity was discovered two decades ago, initially with the designation of Th1 and Th2 cells, which are involved in immunity against intracellular and extracellular pathogens, respectively. Several years ago a third lineage was identified as the Th17 cells and several novel T cell subsets have since been found, including Treg and Tfh cells. The collection of articles presented in the May special issue and accompanying web focus summarize our understanding of the development and function of the T cell subsets in immunity and immune diseases.