한빛사논문
- 조회4,367
Abstract
Delayed Induction, Not Impaired Recruitment of Specific CD8+ T Cells, Causes the Late Onset of Acute Hepatitis C
Eui-Cheol Shin1, 2, Su-Hyung Park1, 2, Mary DeMino2, Michelina Nascimbeni1, 2, Kathleen Mihalik3, Marian Major3, Naga S. Veerapu1, 2, Theo Heller2, Stephen M. Feinstone3, Charles M. Rice4 and Barbara Rehermann1, 2
1 Immunology Section, National Institutes of Health, DHHS, Bethesda, MD 20892
2 Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, DHHS, Bethesda, MD 20892
3 Laboratory of Hepatitis Viruses, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892
4 Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10021
Abstract
Background & Aims
Hepatitis C virus (HCV) infection is characterized by lack of immune-mediated liver injury despite a high level of HCV replication during the incubation phase, which lasts about 8 weeks. We investigated whether this results from delayed recruitment of HCV-specific T cells and whether it facilitates HCV persistence.
Methods
Six chimpanzees were infected with HCV; blood and liver samples were collected for 28 weeks and analyzed for immune cells and chemokines.
Results
Two chimpanzees developed self-limited infections whereas the remaining 4 developed chronic infections. Levels of the chemokines CXCL10, CXCL11, CCL4, and CCL5 increased in blood and liver samples from all chimpanzees within 1 month of HCV infection. Chemokine induction correlated with intrahepatic type I interferon (IFN) responses in vivo and was blocked by neutralizing antibodies against IFN-β in vitro. Despite the early-stage induction of chemokines, the intrahepatic lymphocytic infiltrate started to increase no earlier than 8 weeks after HCV infection, when HCV-specific, tetramer+ CD8+ T cells appeared in the circulation. The HCV-specific CD8+ T cells expressed chemokine receptors when they were initially detected in blood samples, so they could be recruited to the liver as soon as they entered the circulation.
Conclusions
Chemokines are induced during early stages of HCV infection, which requires a type I IFN-mediated response. The delayed onset of acute hepatitis does not result from delayed recruitment of HCV-specific T cells, but could, instead be related to a primary delay in the induction of HCV-specific T cells. Divergent outcomes occur without evident differences in chemokine induction and T-cell recruitment.
Keywords: liver disease; virology; immune response; monkey
Correspondence to Dr. Barbara Rehermann, Immunology Section, Liver Diseases Branch, NIDDK, National Institutes of Health, DHHS, 10 Center Drive, Bldg. 10, Rm. 9B16, Bethesda, MD 20892.
논문정보
- Research article
- 2011년 05월 (BRIC 등록일 )
- 국외 연구진
- 의약학 > 면역의학
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기
