Differing roles of inflammation and antigen in T cell proliferation and memory generation

Recent studies have demonstrated that viral and bacterial infections can in duce dramatic in vivo expansion of Ag-specific T lymphocytes. Although pres entation of Ag is critical for activation of naive T cells, it is less clea r how dependent subsequent in vivo T cell proliferation and memory generati on are upon Ag. We investigated T cell expansion and memory generation in m ice infected alternately with strains of Listeria monocytogenes that contai ned or lacked an immunodominant, MHC class I-restricted T cell epitope, We found substantial differences in the responses of effector and memory T cel ls to inflammatory stimuli, Although effector T cells undergo in vivo expan sion in response to bacterial infection in the absence of Ag, memory T cell s show no evidence for such bystander activation. However, Ag-independent e xpansion of effector T cells does not result in increased memory T cell fre quencies, indicating that Ag presentation is critical for effective memory T cell generation. Early reinfection of mice,vith L, monocytogenes before t he maximal primary T cell response induces typical memory expansion, sugges ting that the capacity for a memory T cell response exists within the prima ry effector population. Our findings demonstrate that T cell effector proli feration and memory generation are temporally overlapping processes,vith di ffering requirements for Ag.