title: Systemic T cell expansion during localized viral infection.
abstract: In a local immune response, the priming and expansion of the antigen-specific T cell population has been thought to largely take place in the draining lymphoid tissue. This model was primarily based on indirect enumeration of antigen-specific T cells by limiting dilution analyses. Here, tetrameric MHC class I complexes were used to evaluate the contribution of different secondary lymphoid organs in a local immune response by following the CD8+ T cell responses against the immunodominant epitopes of influenza A virus and herpes simplex virus-1. Mice were either intranasally infected with influenza A virus and developed pneumonia or were intradermally injected with herpes simplex virus-1. Remarkably, even though these viruses cause a local infection, the spleen of infected animals contains approximately 50-fold more antigen-specific cytotoxic T cells than the draining lymph nodes. Although antigen-specific T cells in spleen appear not to have experienced any recent encounter with antigen, this population is actively dividing, and over time, the formation of a memory T cell population is observed. These data reveal that there is a remarkably large and distinct population of antigen-specific T cells in spleen in the course of a local antigenic challenge. This T cell compartment may not only form the foundation of a memory T cell pool but could also provide a safeguard against systemic spreading of an infection.
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute, Amsterdam.
authors.forename: J B
authors.initials: JB
authors.lastname: Haanen
authors.forename: M
authors.initials: M
authors.lastname: Toebes
authors.forename: T A
authors.initials: TA
authors.lastname: Cordaro
authors.forename: M C
authors.initials: MC
authors.lastname: Wolkers
authors.forename: A M
authors.initials: AM
authors.lastname: Kruisbeek
authors.forename: T N
authors.initials: TN
authors.lastname: Schumacher
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006561:Herpes Simplex / Q000276:immunology*; D009980:Influenza A virus; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology*; D014758:Viral Core Proteins / Q000276:immunology
chemical_list: D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010446:Peptide Fragments; D014758:Viral Core Proteins