title: Prolonged activation of virus-specific CD8+T cells after acute B19 infection.
abstract: BACKGROUND
  Human parvovirus B19 (B19) is a ubiquitous and clinically significant pathogen, causing erythema infectiosum, arthropathy, transient aplastic crisis, and intrauterine fetal death. The phenotype of CD8+ T cells in acute B19 infection has not been studied previously.
  
  
  RESULTS
  The number and phenotype of B19-specific CD8+ T cell responses during and after acute adult infection was studied using HLA-peptide multimeric complexes. Surprisingly, these responses increased in magnitude over the first year post-infection despite resolution of clinical symptoms and control of viraemia, with T cell populations specific for individual epitopes comprising up to 4% of CD8+ T cells. B19-specific T cells developed and maintained an activated CD38+ phenotype, with strong expression of perforin and CD57 and downregulation of CD28 and CD27. These cells possessed strong effector function and intact proliferative capacity. Individuals tested many years after infection exhibited lower frequencies of B19-specific cytotoxic T lymphocytes, typically 0.05%-0.5% of CD8+ T cells, which were perforin, CD38, and CCR7 low.
  
  
  CONCLUSIONS
  This is the first example to our knowledge of an "acute" human viral infection inducing a persistent activated CD8+ T cell response. The likely explanation--analogous to that for cytomegalovirus infection--is that this persistent response is due to low-level antigen exposure. CD8+ T cells may contribute to the long-term control of this significant pathogen and should be considered during vaccine development.
authors.affiliation: Institution for Medicine, Infectious Disease Unit, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. adiba.isa@cmm.ki.se
authors.forename: Adiba
authors.initials: A
authors.lastname: Isa
authors.forename: Victoria
authors.initials: V
authors.lastname: Kasprowicz
authors.forename: Oscar
authors.initials: O
authors.lastname: Norbeck
authors.forename: Andrew
authors.initials: A
authors.lastname: Loughry
authors.forename: Katie
authors.initials: K
authors.lastname: Jeffery
authors.forename: Kristina
authors.initials: K
authors.lastname: Broliden
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
authors.forename: Thomas
authors.initials: T
authors.lastname: Tolfvenstam
authors.forename: Paul
authors.initials: P
authors.lastname: Bowness
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000096:biosynthesis; D000208:Acute Disease; D018106:CD28 Antigens / Q000096:biosynthesis; D018959:CD57 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015536:Down-Regulation; D016731:Erythema Infectiosum / Q000276:immunology*; D006801:Humans; D016732:Parvovirus B19, Human / Q000472:pathogenicity*; D010641:Phenotype; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis
chemical_list: D018106:CD28 Antigens; D018959:CD57 Antigens; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D051997:ADP-ribosyl Cyclase 1