Sustained response initiation is required for T cell clonal expansion but not for effector or memory development in vivo.

The factors determining whether an immune response is productive are poorly understood. To understand the circumstances affecting the early stage of the immune response which determine whether memory is generated, the CD8 T cell response was mapped in detail following immunization with live or heat-killed bacteria. Our results demonstrate that even in response to a weak immunogen, functional memory cell development is linked to effector cell induction in lymphoid and nonlymphoid tissues. The main defect in the response to killed microorganisms is inefficient induction of clonal expansion. This failure is due to a contracted, but costimulation-dependent activation phase in the lymphoid tissues, resulting in rapid but abortive growth. Conversely, the response to live bacteria is characterized by protracted early T cell sequestration in lymphoid tissues. Thus, memory development requires effector induction, while optimal clonal expansion is regulated by the duration of response initiation.