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Differentiation and Protective Capacity of Virus-Specific CD8+ T Cells Suggest Murine Norovirus Persistence in an Immune-Privileged Enteric Niche.
Tomov, Vesselin T; Palko, Olesya; Lau, Chi Wai; Pattekar, Ajinkya; Sun, Yuhang; Tacheva, Ralitza; Bengsch, Bertram; Manne, Sasikanth; Cosma, Gabriela L; Eisenlohr, Laurence C; Nice, Timothy J; Virgin, Herbert W; Wherry, E John.
Afiliação
  • Tomov VT; Department of Medicine, Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. Electronic address: tomovv@pennmedicine.upenn.edu.
  • Palko O; Department of Medicine, Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
  • Lau CW; Department of Medicine, Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
  • Pattekar A; Department of Medicine, Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
  • Sun Y; Department of Medicine, Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
  • Tacheva R; Department of Medicine, Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
  • Bengsch B; Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
  • Manne S; Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
  • Cosma GL; Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
  • Eisenlohr LC; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia Research Institute and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
  • Nice TJ; Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USA.
  • Virgin HW; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Wherry EJ; Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. Electronic address: wherry@pennmedicine.upenn.edu.
Immunity ; 47(4): 723-738.e5, 2017 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-29031786
ABSTRACT
Noroviruses can establish chronic infections with active viral shedding in healthy humans but whether persistence is associated with adaptive immune dysfunction is unknown. We used genetically engineered strains of mouse norovirus (MNV) to investigate CD8+ T cell differentiation during chronic infection. We found that chronic infection drove MNV-specific tissue-resident memory (Trm) CD8+ T cells to a differentiation state resembling inflationary effector responses against latent cytomegalovirus with only limited evidence of exhaustion. These MNV-specific Trm cells remained highly functional yet appeared ignorant of ongoing viral replication. Pre-existing MNV-specific Trm cells provided partial protection against chronic infection but largely ceased to detect virus within 72 hours of challenge, demonstrating rapid sequestration of viral replication away from T cells. Our studies revealed a strategy of immune evasion by MNV via the induction of a CD8+ T cell program normally reserved for latent pathogens and persistence in an immune-privileged enteric niche.
Assuntos
Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Diferenciação Celular / Infecções por Caliciviridae / Linfócitos T CD8-Positivos / Norovirus / Gastroenterite Limite: Animais / Humanos Idioma: Inglês Revista: Immunity Assunto da revista: Alergia e Imunologia Ano de publicação: 2017 Tipo de documento: Artigo

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Diferenciação Celular / Infecções por Caliciviridae / Linfócitos T CD8-Positivos / Norovirus / Gastroenterite Limite: Animais / Humanos Idioma: Inglês Revista: Immunity Assunto da revista: Alergia e Imunologia Ano de publicação: 2017 Tipo de documento: Artigo