Molecular and immunological study on the pathogenesis of hepatitis C

在本研究中，我们证明了HLAB 44阳性的丙型肝炎患者对HCV核心抗原a.a. 88-96患者血清HCVRNA水平较低，提示CTL可抑制HCV的生长。因此，HCV感染的CTL应答不足以清除病毒。a. 88-96型仅在27例HLA B44阳性患者中观察到3例。3种变异体均能被CTL有效识别，但其中2种变异体不能有效诱导CTL，另1种变异体能诱导CTL，而且当少量变异体HCV与野生型HCV共存时，特异性CTL识别特异性变异表位的诱导作用被抑制，HCV特异性CTL通过前体-、Fas配体-和Fas配体-识别并杀伤HCV感染的靶细胞。基于TNF的机制。此外，激活的CTL通过Fas配体和基于TNF的机制杀死旁观者敏感的未感染细胞。这些机制可能有助于肝脏炎症的扩大。

In the present study, we demonstrated that HLA B44-positive hepatitis C patients with demonstarable CTL response to HCV core antigen a.a. 88-96 had lower levels of serum HCV RNA, suggesting that CTL may suppress the outgrowth of HCV.In addition, CTh response was observed to multiple HCV epitopes in the same patients. Thus CTL response to HCV infection is not strong enough to eliminate the virus.The variation of amino acid in HCV core a. a. 88-96 was observed only 3 of 27 HLA B44-positive patients. All three variants could be recognized by CTL as effectively as wild-type HCV antigen, but two of three variants could not induce CTL effectively while the other one could induce CTL.Furthermore, when a small amount of variant HCV co-existed with wild-type HCV, the induction of CTL recognizing spesifically variant epitope was sppressed.HCV-specific CTL recognized and killed HCV-infected target cells by perform-, Fas ligand-, and. TNF-based mechanisms. In addition, activated CTL killed bystander sensitive non-infected cells by Fas ligand and TNF-based mechanisms. The mechanisms may contribute to the expansion of inflammation in the liver.