Induction of HCV-specific CTLs upon SFV immunizations. Mice were primed
and boosted intramuscularly with (a) 5 × 106 or
105 SFV-NS3/4A or SFV-sHELP-NS3/4A infectious particles,
(b) to (d) 5 × 106 SFV-NS5A/B or SFV-sHELP-NS5A/B infectious
particles, or PBS at a 2 week interval. Mice were sacrificed 10 days
after the last immunization, and splenocytes were isolated for an
in vitro cytotoxicity assay (a) to (c) and
intracellular cytokine staining using flow cytometry (d). (a) Isolated
splenocytes were cultured with Hepa1-6VenusnsPs cells at a
ratio of 25:1. After a 7 day culture, splenocytes were co-cultured for
4 h with 51Cr labeled target EL4 cells pulsed with GAVQNEVTL
peptide at 25:1 ratio. (b) and (c) Isolated splenocytes were cultured
with Hepa1-6VenusNS5A/B cells at a ratio of 25:1. After a 7
day culture, splenocytes were co-cultured for 4 h with 51Cr
labeled target EL4 cells pulsed with ILDSFDPL peptide or
EL4-VENUS-NS5A/B at the indicated E:T ratios. (d)
Splenocytes were stimulated with ILDSFDPL for 4 h and subjected to
surface and intracellular cytokine staining. The frequencies of
IFN–γ+CD107a/b+ within the CD8+ T
cells are shown. Data represent mean ± SEM (n = 3–5).
*p < 0.05.