DISTINCT COSTIMULATORY MOLECULES ARE REQUIRED FOR THE INDUCTION OF EFFECTOR AND MEMORY CYTOTOXIC T-LYMPHOCYTES

A successful T cell immune response has two major products: effector T cells which directly or indirectly remove the antigens, and memory T cells, which allow a faster and more efficient recall response when ch allenged by related antigens. An important issue is whether costimulat ory molecules on the antigen-presenting cells are involved in determin ing whether T cells will differentiate into effector or memory cells a fter antigenic stimulation. To address this issue, we have produced mi ce with targeted mutations of either the heat-stable antigen (HSA), or both HSA and CD28. We show that CD28/B7 and HSA provide two alternati ve costimulatory pathways for induction of immunological memory to inf luenza virus. Furthermore, our results revealed that B7 is essential f or the generation of effector T cells from either naive or memory T ce lls, while HSA is not necessary for the generation of effector T cells . Our results demonstrate that the induction of memory T cells and eff ector T cells can utilize distinct costimulatory molecules. These resu lts have important implications on Lineage relationship between effect or and memory T cells.