Cellular Immune Response to Hantaan Virus Nucleocapsid Protein in the Acute Phase of Hemorrhagic Fever with Renal Syndrome: Correlation with Disease Severity

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, <= 707 mu mol/L) than in those with subsequent severe renal failure (maximum serum creatinine level, > 707 mu mol/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. Conclusion. 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.