Differing roles of inflammation and antigen in T cell proliferation and memory generation.
Recent studies have demonstrated that viral and bacterial infections can induce dramatic in vivo expansion of Ag-specific T lymphocytes. Although presentation of Ag is critical for activation of naive T cells, it is less clear how dependent subsequent in vivo T cell proliferation and memory generation are upon Ag. We investigated T cell expansion and memory generation in mice infected alternately with strains of Listeria monocytogenes that contained or lacked an immunodominant, MHC class I-restricted T cell epitope. We found substantial differences in the responses of effector and memory T cells to inflammatory stimuli. Although effector T cells undergo in vivo expansion in response to bacterial infection in the absence of Ag, memory T cells show no evidence for such bystander activation. However, Ag-independent expansion of effector T cells does not result in increased memory T cell frequencies, indicating that Ag presentation is critical for effective memory T cell generation. Early reinfection of mice with L. monocytogenes before the maximal primary T cell response induces typical memory expansion, suggesting that the capacity for a memory T cell response exists within the primary effector population. Our findings demonstrate that T cell effector proliferation and memory generation are temporally overlapping processes with differing requirements for Ag.
Busch
D H
DH
Sections of Infectious Diseases and Immunobiology, Yale University School of Medicine, New Haven, CT 06511, USA.
Kerksiek
K M
KM
Pamer
E G
EG
D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002455:Cell Division / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D007156:Immunologic Memory / Q000276:immunology*; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007700:Kinetics; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology
D000942:Antigens, Bacterial; D018984:Epitopes, T-Lymphocyte