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Specificity and dynamics of effector and memory CD8 T cell responses in human tick-borne encephalitis virus infection.
Blom, Kim; Braun, Monika; Pakalniene, Jolita; Dailidyte, Laura; Béziat, Vivien; Lampen, Margit H; Klingström, Jonas; Lagerqvist, Nina; Kjerstadius, Torbjörn; Michaëlsson, Jakob; Lindquist, Lars; Ljunggren, Hans-Gustaf; Sandberg, Johan K; Mickiene, Aukse; Gredmark-Russ, Sara.
Afiliación
  • Blom K; Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
  • Braun M; Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
  • Pakalniene J; Department of Infectious Diseases, Lithuanian University of Health Sciences, Kaunas, Lithuania.
  • Dailidyte L; Department of Infectious Diseases, Lithuanian University of Health Sciences, Kaunas, Lithuania.
  • Béziat V; 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.
  • Lampen MH; Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
  • Klingström J; Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
  • Lagerqvist N; Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
  • Kjerstadius T; Karolinska University Laboratory, Department of Clinical Microbiology, Karolinska University Hospital Solna, Stockholm, Sweden.
  • Michaëlsson J; Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
  • Lindquist L; 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.
  • Ljunggren HG; Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
  • Sandberg JK; Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
  • Mickiene A; 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.
  • Gredmark-Russ S; 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.
PLoS Pathog ; 11(1): e1004622, 2015 Jan.
Article en En | MEDLINE | ID: mdl-25611738
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T CD8-positivos / Especificidad del Receptor de Antígeno de Linfocitos T / Encefalitis Transmitida por Garrapatas / Virus de la Encefalitis Transmitidos por Garrapatas / Memoria Inmunológica Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: PLoS Pathog Año: 2015 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Estados Unidos
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T CD8-positivos / Especificidad del Receptor de Antígeno de Linfocitos T / Encefalitis Transmitida por Garrapatas / Virus de la Encefalitis Transmitidos por Garrapatas / Memoria Inmunológica Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: PLoS Pathog Año: 2015 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Estados Unidos