title: Antigen-specific naive CD8+ T cells produce a single pulse of IFN-γ in vivo within hours of infection, but without antiviral effect.
abstract: In vitro studies have shown that naive CD8(+) T cells are unable to express most of their effector proteins until after at least one round of cell division has taken place. We have reassessed this issue in vivo and find that naive CD8(+) T cells mount Ag-specific responses within hours of infection, before proliferation has commenced. Newly activated naive Ag-specific CD8(+) T cells produce a rapid pulse of IFN-γ in vivo and begin to accumulate granzyme B and perforin. Later, in vivo cytolytic activity is detectable, coincident with the initiation of cell division. Despite the rapid development of these functional attributes, no antiviral effect was observed early during infection, even when the cells are present in numbers similar to those of virus-specific memory cells. The evolutionary reason for the pulse of IFN-γ synthesis by naive T cells is uncertain, but the lack of antiviral impact suggests that it may be regulatory.
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037 mhosking@scripps.edu.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Hosking
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037.
authors.forename: Claudia T
authors.initials: CT
authors.lastname: Flynn
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037.
authors.forename: J Lindsay
authors.initials: JL
authors.lastname: Whitton
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D053804:Granzymes / Q000096:biosynthesis; D007156:Immunologic Memory / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054353:Perforin / Q000096:biosynthesis; D020825:T-Box Domain Proteins / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014779:Virus Replication / Q000276:immunology; D000098815:T-bet Transcription Factor
chemical_list: C491198:Eomes protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; D007371:Interferon-gamma; D053804:Granzymes