Schistosoma infection inhibits cellular immune responses to core HCV peptides

SUMMARY Patients coinfected with hepatitis C virus (HCV) and the trematode, Schistosoma mansoni , have an increased incidence of viral persistence and accelerated fibrosis. To investigate immunological mechanisms responsible for this more aggressive natural history of HCV, the core HCV-specific T-cell responses were analysed in 44 donated blood units rejected because they had antibodies to HCV (anti-HCV). Half also had antiS. mansoni antibodies, evidence of past or active infection. HCV-specific ELISPOT responses were examined using pools of 180 overlapping 9-mer peptides with offsets of one covering the core of HCV genotype 4a. Comparison of T-cell responses in blood units positive for both anti-HCV and anti -Schistosoma antibodies with blood units positive only for anti-HCV antibodies showed a significant decrease in core-specific T-cell IFN- γ (505 ± 46 vs. 803 ± 66 ISC/10 6 cells, P < 0·001), IL-4 (2 ± 108 vs. 641 ± 131 ISC/10 6 cells, P < 0·001), and IL-10 (159 ± 105 vs. 466 ± 407 ISC/10 6 cells, P < 0·002) responses. In contrast, there was no significant difference in cellmediated immune response (CMI) to PHA mitogen between these two groups. Therefore, we concluded T cells from persons with anti- Schistosoma have reduced IFN- γ , IL-4, and IL-10 secreting HCV-specific T-cell responses. This may explain why Schistosoma coinfection increases persistence and severity of HCV infection .