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After activation, CD4 helper T (Th) cells differentiate into Th1 or Th2 effector subsets. These two types of cells produce distinct profiles of cytokines and regulate different immune responses. This review summarizes recent progress on different features of co-stimulatory regulation and chemokine-mediated homing of Th1 and Th2 cells. Transcription factors and signaling pathways that are selectively expressed or activated in Th1 and Th2 cells to regulate cytokine gene expression are discussed.