title: Cellular immune response to Hantaan virus nucleocapsid protein in the acute phase of hemorrhagic fever with renal syndrome: correlation with disease severity.
abstract: BACKGROUND
  The cellular immune response to Hantaan virus (HTNV) is incompletely understood, especially in humans.
  
  
  METHODS
  To investigate the cellular immunity during acute HTNV infection, the magnitude of the CD4(+) and CD8(+) T cell responses to HTNV nucleocapsid protein was quantitated by direct ex vivo interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot analysis, using an array of overlapping peptides.
  
  
  RESULTS
  We found that the combined frequencies of HTNV-specific T cells at the earliest available time point (5-8 days after fever onset) were significantly higher in patients who had mild or moderate hemorrhagic fever with renal syndrome (HFRS) than in those who had severe or critical HFRS (P= .006). Moreover, these frequencies were higher in patients with subsequent mild renal failure (maximum serum creatinine level, <or=707 micromol/L) than in those with subsequent severe renal failure (maximum serum creatinine level, >707 micromol/L) (P= .006). Kinetic analysis showed that a decrease in the serum creatinine level during the acute phase of illness was often accompanied by an increase in the magnitude of IFN-gamma-producing T cells.
  
  
  CONCLUSIONS
  Taken together with published data on the similar associations with neutralizing antibody, these data suggest that IFN-gamma-producing T cells may help reduce the risk of progression to acute renal failure caused by HTNV infection.
authors.affiliation: Department of Immunology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Meiliang
authors.initials: M
authors.lastname: Wang
authors.forename: Jiuping
authors.initials: J
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
authors.forename: Zhuwei
authors.initials: Z
authors.lastname: Xu
authors.forename: Kun
authors.initials: K
authors.lastname: Yang
authors.forename: Angang
authors.initials: A
authors.lastname: Yang
authors.forename: Boquan
authors.initials: B
authors.lastname: Jin
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D036022:Capsid Proteins / Q000276:immunology*; D002681:China; D005260:Female; D018063:Hantaan virus / Q000276:immunology*; D006480:Hemorrhagic Fever with Renal Syndrome / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D014758:Viral Core Proteins / Q000276:immunology*; D055815:Young Adult
chemical_list: D036022:Capsid Proteins; D014758:Viral Core Proteins; C111782:nucleocapsid protein, Hantaan virus; D007371:Interferon-gamma