Quantitative and qualitative characteristics of the signals received by a T cell determine whether receptor ligation results in cell activation, cell death, or the induction of antigen-specific non-responsiveness. Environmental factors such as the nature of costimulation, antigen-presenting cell type, peptide structure and cytokine levels also influence the differentiation of CD4+ helper T cells into functionally distinct subsets, which now appear pivotal in many immune-mediated disorders, including autoimmunity and allergy. Selective manipulation of the immune response, such as the functional inactivation or deviation of the cytokine secretion patterns of specific T cells, may be an effective strategy for immunotherapy.