title: Specificity and dynamics of effector and memory CD8 T cell responses in human tick-borne encephalitis virus infection.
abstract: Tick-borne encephalitis virus (TBEV) is transferred to humans by ticks. The virus causes tick-borne encephalitis (TBE) with symptoms such as meningitis and meningoencephalitis. About one third of the patients suffer from long-lasting sequelae after clearance of the infection. Studies of the immune response during TBEV-infection are essential to the understanding of host responses to TBEV-infection and for the development of therapeutics. Here, we studied in detail the primary CD8 T cell response to TBEV in patients with acute TBE. Peripheral blood CD8 T cells mounted a considerable response to TBEV-infection as assessed by Ki67 and CD38 co-expression. These activated cells showed a CD45RA-CCR7-CD127- phenotype at day 7 after hospitalization, phenotypically defining them as effector cells. An immunodominant HLA-A2-restricted TBEV epitope was identified and utilized to study the characteristics and temporal dynamics of the antigen-specific response. The functional profile of TBEV-specific CD8 T cells was dominated by variants of mono-functional cells as the effector response matured. Antigen-specific CD8 T cells predominantly displayed a distinct Eomes+Ki67+T-bet+ effector phenotype at the peak of the response, which transitioned to an Eomes-Ki67-T-bet+ phenotype as the infection resolved and memory was established. These transcription factors thus characterize and discriminate stages of the antigen-specific T cell response during acute TBEV-infection. Altogether, CD8 T cells responded strongly to acute TBEV infection and passed through an effector phase, prior to gradual differentiation into memory cells with distinct transcription factor expression-patterns throughout the different phases.
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Kim
authors.initials: K
authors.lastname: Blom
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Monika
authors.initials: M
authors.lastname: Braun
authors.affiliation: Department of Infectious Diseases, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Jolita
authors.initials: J
authors.lastname: Pakalniene
authors.affiliation: Department of Infectious Diseases, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Laura
authors.initials: L
authors.lastname: Dailidyte
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; Human Genetics of Infectious Diseases Laboratory, Imagine Institute-INSERM U1163, Paris, France.
authors.forename: Vivien
authors.initials: V
authors.lastname: Béziat
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Margit H
authors.initials: MH
authors.lastname: Lampen
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Klingström
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Nina
authors.initials: N
authors.lastname: Lagerqvist
authors.affiliation: Karolinska University Laboratory, Department of Clinical Microbiology, Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Kjerstadius
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Jakob
authors.initials: J
authors.lastname: Michaëlsson
authors.affiliation: Department of Infectious Diseases, Karolinska University Hospital Huddinge, Stockholm, Sweden; Unit of Infectious Disease, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Lindquist
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Hans-Gustaf
authors.initials: HG
authors.lastname: Ljunggren
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Johan K
authors.initials: JK
authors.lastname: Sandberg
authors.affiliation: Department of Infectious Diseases, Lithuanian University of Health Sciences, Kaunas, Lithuania; Unit of Infectious Disease, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Aukse
authors.initials: A
authors.lastname: Mickiene
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Infectious Diseases, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Gredmark-Russ
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D004669:Encephalitis Viruses, Tick-Borne / Q000276:immunology*; D004675:Encephalitis, Tick-Borne / Q000276:immunology*; D018604:Epitope Mapping; D015789:HLA-A2 Antigen / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007156:Immunologic Memory / Q000502:physiology*; D008213:Lymphocyte Activation; D037182:T-Cell Antigen Receptor Specificity
chemical_list: D015789:HLA-A2 Antigen; D016056:Immunodominant Epitopes