The development of effector and memory populations of T lymphocytes is determined by antigen-induced growth and differentiation of naive T cells, and it is regulated by antigen-induced functional tolerance and cell death. CD4+ helper T lymphocytes that vary in their profiles of cytokine production and in effector functions also show distinct responses to antigens and co-stimulatory signals, and they differ in their sensitivity to tolerance induction. Thus, stimuli that trigger T cell growth and differentiation, as well as mechanisms that inhibit T cell expansion, determine both the magnitude and the nature of T cell-dependent immune responses to protein antigens.