title: Reduced naive CD4 T cell numbers and impaired induction of CD27 in response to T cell receptor stimulation reflect a state of immune activation in chronic hepatitis C virus infection.
abstract: BACKGROUND
  Chronic hepatitis C virus (HCV) infection is characterized by reduced numbers of functional HCV-specific T cells. In addition, chronically HCV-infected individuals have reduced response to vaccine. Alterations in naive CD4 T cell phenotype or function may contribute to these immune impairments.
  
  
  METHODS
  Using flow cytometric analysis and enzyme-linked immunospot assay, we examined peripheral naive CD4 T cell phenotype and function in chronically HCV-infected patients and control subjects.
  
  
  RESULTS
  We observed significantly lower absolute cell numbers of naive CD4 T cells in HCV-infected patients, localized to the CD127(+)CD25(low/-) and CD31(+) (RTE) subsets. Moreover, we found greater percentages of naive cells expressing CD25 and KI67 in HCV-infected patients, consistent with immune activation, further supported by higher plasma sCD27 levels. Functional analysis revealed an intact interferon-γ response to allogeneic B cell stimulus. However, after direct TCR stimulation, naive CD4 T cells from HCV-infected patients had altered up-regulation of KI67 and CD25 and less CD27 expression. The latter was associated with elevated baseline activation state. In addition, naive CD4 T cells from HCV-infected patients were more susceptible to cell death.
  
  
  CONCLUSIONS
  These numerical and functional defects may contribute to inadequate formation of virus and neoantigen-specific T cell responses during chronic HCV infection.
authors.affiliation: Department of Pathology, Division of Infectious and Rheumatic Diseases, University Hospitals Case Medical Center, Cleveland, Ohio, USA.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Yonkers
authors.forename: Scott
authors.initials: S
authors.lastname: Sieg
authors.forename: Benigno
authors.initials: B
authors.lastname: Rodriguez
authors.forename: Donald D
authors.initials: DD
authors.lastname: Anthony
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood / Q000276:immunology* / Q000821:virology; D006801:Humans; D007371:Interferon-gamma; D008297:Male; D008875:Middle Aged; D009820:Ohio; D011948:Receptors, Antigen, T-Cell / Q000097:blood / Q000276:immunology*; D012307:Risk Factors; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis*
chemical_list: D011948:Receptors, Antigen, T-Cell; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D007371:Interferon-gamma