title: Human dendritic cells infected with the nonpathogenic Mopeia virus induce stronger T-cell responses than those infected with Lassa virus.
abstract: The events leading to death in severe cases of Lassa fever (LF) are unknown. Fatality seems to be linked to high viremia and immunosuppression, and cellular immunity, rather than neutralizing antibodies, appears to be essential for survival. We previously compared Lassa virus (LV) with its genetically close but nonpathogenic homolog Mopeia virus (MV), which was used to model nonfatal LF. We showed that strong and early activation of antigen-presenting cells (APC) may play a crucial role in controlling infection. Here we developed an in vitro model of dendritic-cell (DC)-T-cell coculture in order to characterize human T-cell responses induced by MV- or LV-infected DCs. Our results show very different responses to infection with LV and MV. MV strongly and durably stimulated CD8(+) and CD4(+) T cells, showing early and high activation, a strong proliferative response, and acquisition of effector and memory phenotypes. Furthermore, robust and functional CD4(+) and CD8(+) cytotoxic T lymphocytes (CTL) were generated. LV, however, induced only weak memory responses. Thus, this study allows an improved understanding of the pathogenesis and immune mechanisms involved in the control of human LV.
authors.affiliation: Unité de Biologie des Infections Virales Emergentes, Institut Pasteur, Lyon Cedex 07, France. sylvain.baize@inserm.fr
authors.forename: Delphine
authors.initials: D
authors.lastname: Pannetier
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Reynard
authors.forename: Marion
authors.initials: M
authors.lastname: Russier
authors.forename: Alexandra
authors.initials: A
authors.lastname: Journeaux
authors.forename: Noël
authors.initials: N
authors.lastname: Tordo
authors.forename: Vincent
authors.initials: V
authors.lastname: Deubel
authors.forename: Sylvain
authors.initials: S
authors.lastname: Baize
mesh_terms: D018049:Arenaviruses, Old World / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D007836:Lassa virus / Q000276:immunology; D008213:Lymphocyte Activation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D016207:Cytokines