Abstract
When activated, CD4^+^ T cells differentiate into two major sub‐populations differing in their profiles of secreted cytokines. Type One, or TH1, cells secrete IL‐2, IFNγ, and TNFβ and mediate a cellular immune response. Type Two, or TH2, cells secrete IL‐4, IL‐5, IL‐6, IL‐10, and IL‐13 and potentiate a humoral response. The nature of any specific immune response depends on the interaction of antigen‐presenting cells and T cells. The role of antigen‐presenting cells is to respond to the nature of the immune challenge and signal differentiation of CD4^+^ T cells. A number of factors are involved in the effector phenotype of T cells—nature and affinity of antigen, co‐receptors signals, and cytokine environment. T‐cell differentiation is a complex process comprising four defined developmental stages: activation of particular cytokine genes, commitment of the cells, silencing of the opposing cytokine genes, and stabilization of the phenotype. In each of these stages, the cells respond to the products of many signaling cascades from many membrane‐bound receptors. The stages in development are mediated by different molecular mechanisms, involving control of gene expression and chromatin remodeling. This review centers on the factors, cellular interactions, and molecular mechanisms involved in the maturation of naïve CD4^+^ T lymphocytes into fully effector cells. © 2003 Wiley‐Liss, Inc.