Progressive differentiation and selection of the fittest in the immune response.

T cells are stimulated by stochastic exposure to antigen-presenting cells and cytokines. We review evidence that the level of signal that is accumulated determines progression through hierarchical thresholds for proliferation and differentiation, leading to the generation of various intermediates and effector T cells. These cells are then selected to enter the memory pool according to their fitness--that is, their capacity to access and use survival signals. We suggest that the intermediates that are generated by antigenic stimulation of T and B cells persist as central memory cells, which can mount secondary responses to antigen and maintain appropriate levels of effector cells and antibodies throughout the lifetime of an individual.