| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
Recent studies have shown that tumor necrosis factor-α (TNF-α) plays critical roles in viral clearance but also lymphoid tissue development and stem cell differentiation. In this study, we attempted to induce hepatitis B virus (HBV)-specific CTLs by immunization of TNF-α knockout (TNF-α^<-/->) mice with HBsAg-encoding plasmid DNA. An immunization with a single failed to induce CTL responses in TNF-α^<-/-> mice, although CTLs were readily induced in wild-type mice using the same protocol. Weak CTL responses were produced in TNF-α^<-/-> mice after two sessions with HBV-plasmid immunization ; however, TNF-α was required to maintain the responses of these CTL lines to in vitro stimulation and, even then, the responses were lost after 3 weeks. Interestingly, limiting dilution of a CTL line showed that HBV-specific CTL clones with high specific cytotoxicity were present in TNF-α^<-/-> mice, but these clones again failed to proliferate for more than 3 weeks. Furthermore, since exogeneously added TNF-α enhanced the proliferation of TNF-α^<-/-> clone but suppressed that of TNF-α^<+/+> clone in vitro, TNF-α also has a direct effect on the proliferation of CTLs. In conclusion, TNF-α plays an essential role in the induction and proliferation of virus-specific CTLs both in vivo and in vitro.
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