title: Qualitatively different memory CD8+ T cells are generated after lymphocytic choriomeningitis virus and influenza virus infections.
abstract: Viral infections often induce robust T cell responses that are long-lived and protective. However, it is unclear to what degree systemic versus mucosal infection influences the generation of effector and memory T cells. In this study, we characterized memory CD8(+) T cells generated after respiratory influenza virus infection and compared the phenotypic and functional qualities of these cells with memory T cells generated after systemic infection with lymphocytic choriomeningitis virus (LCMV). Using a recombinant influenza virus expressing the LCMV gp(33-41) epitope and TCR transgenic CD8(+) T cells with a fixed TCR, we compared responses to the same Ag delivered by mucosal or systemic viral infection. Memory cells generated postinfection with either virus showed only a few phenotypic differences. Yet, influenza memory T cells produced lower amounts of effector cytokines upon restimulation and displayed reduced proliferation compared with LCMV-induced memory cells. Strikingly, we observed reduced expansion of spleen- and, in particular, lung-derived influenza memory cells after recall in vivo, which correlated with reduced early protection from secondary infection. These findings suggest that qualitatively different memory CD8(+) T cells are generated after respiratory or systemic virus infections.
authors.affiliation: Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA. smue@unimelb.edu.au
authors.forename: Scott N
authors.initials: SN
authors.lastname: Mueller
authors.forename: William A
authors.initials: WA
authors.lastname: Langley
authors.forename: Guimei
authors.initials: G
authors.lastname: Li
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Webby
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000378:metabolism; D004274:DNA, Recombinant / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000821:virology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014709:Vero Cells
chemical_list: D016207:Cytokines; D004274:DNA, Recombinant