Costimulation for Immunological Memory
A successful T cell immune response has two major products: effector T cells which eliminate infection, and memory T cells which, although have no immediate effector function, mount a faster and more potent immune response when re-encounter related antigens. The molecular and cellular interactions leading to the two products are not well understood at the present. We are investigating the role of two costimulatory pathways, namely that mediated by B7:CD28 interaction, and that mediated by the heat-stable antigen (HSA), in the induction of immunological memory. We will study two questions. First, using mice with targeted mutation of either HSA or CD28, we will test whether the production of effector and memory T cells requires distinct costimulatory molecules. Second, we will carry out lineage-ablation experiments to test whether effector T cells are precursors for memory T cells. We will also determine whether the memory T cells that are induced via distinct costimulatory molecules are produced by different differentiation pathways. Our proposed studies will facilitate the understanding of the molecular mechanism of immunological memory and should have important implications on cell-fate determination during immune response.