HCV Persistence and Immune Evasion in the Absence of Memory T Cell Help

American Association for the Advancement of Science (AAAS) - Tập 302 Số 5645 - Trang 659-662 - 2003
Arash Grakoui1,2,3,4,5, Naglaa H. Shoukry1,2,3,4,5, David J. Woollard1,2,3,4,5, Jin‐Hwan Han1,2,3,4,5, Holly L. Hanson1,2,3,4,5, John Ghrayeb1,2,3,4,5, Krishna K. Murthy1,2,3,4,5, Charles M. Rice1,2,3,4,5, Christopher M. Walker1,2,3,4,5
1Center for Vaccines and Immunity, Columbus Children's Research Institute, 700 Children's Drive, W503, Columbus, OH 43205, USA.
2Center for the Study of Hepatitis C, Rockefeller University, New York, NY 10021, USA.
3Centocor, Malvern, PA 19355, USA.
4Department of Pediatrics, College of Medicine and Public Health, Ohio State University, Columbus, OH 43205, USA.
5Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, TX 78227, USA.

Tóm tắt

Spontaneous resolution of hepatitis C virus (HCV) infection in humans usually affords long-term immunity to persistent viremia and associated liver diseases. Here, we report that memory CD4 + Tcells are essential for this protection. Antibody-mediated depletion of CD4 + Tcells before reinfection of two immune chimpanzees resulted in persistent, low-level viremia despite functional intra-hepatic memory CD8 + Tcell responses. Incomplete control of HCV replication by memory CD8 + Tcells in the absence of adequate CD4 + Tcell help was associated with emergence of viral escape mutations in class I major histocompatibility complex–restricted epitopes and failure to resolve HCV infection.

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Supported by Public Health service grants to C.M.W. (A147367 and AI48231) and C.M.R. (CA57973 CA85883 and AI40034) and the Greenberg Medical Research Institute. NIH contract N01 HB27091 to K.K.M. is also gratefully acknowledged. A.G. is supported by a Cancer Research Institute Postdoctoral Fellowship award. N.H.S. is the recipient of postdoctoral fellowships from the Canadian Institute for Health Research and the American Liver Foundation. We thank D. Hasselschwert and N. Smith of the New Iberia Research Center New Iberia LA for outstanding veterinary support; D. Conway for superb technical assistance; and J. Stacey for critical reading of the manuscript.

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American Association for the Advancement of Science (AAAS)

Tập 302 Số 5645

659-662

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