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EXPOSURE TO HEPATITIS C VIRUS INDUCES CELLULAR IMMUNE RESPONSES WITHOUT DETECTABLE VIREMIA OR SEROCONVERSION

Sporadic cases of cell-mediated immunity (CMI) in persons exposed to hepatitis C (HCV) but evidently uninfected have been reported. To further define this, we measured CMI in individuals without evidence of HCV infection, that is, negative for HCV-antibodies (anti-HCV) and RNA, residing in a rural Egyptian community where prevalence of anti-HCV was 24%. Cell-mediated immunity (CMI) measured by interferon-gamma (IFN-) enzyme-linked immunospot (ELISPOT) assay, confirmed by intracellular staining using flow cytometry, against HCV peptides was measured in seronegative individuals with high-risk (HR) and low-risk (LR) exposures to HCV. Thirteen of 71 (18.3%) HR subjects but only 1 of 35 (2.9%) LR subjects had detectable CMI (P = 0.032). These data are compatible with the hypothesis that exposures to HCV may lead to development of HCV-specific CMI without anti-HCV and ongoing viral replication. We speculate induced CMI clears HCV sometimes when anti-HCV is not detectable, and HCV-specific CMI is a useful surrogate marker for exposure to HCV.

Received November 17, 2004. Accepted for publication February 8, 2005.

Acknowledgments: We appreciate the advice of Dr. Paul Hagan and the dedicated assistance of the professional and technical staffs at CFAR, ERDC, and VHRL in Cairo, at the NYBC in New York City, and at the IRBM in Rome in the conduct of these studies. Mar Jan Ostrowski and his administrative staff at the HCP Project in Egypt provided invaluable administrative, financial, and logistic support, and Kelly Weed provided editorial assistance.

Financial support: The research was supported in part by NIH grant RO1-AI47349, the Wellcome Trust-Burroughs Wellcome Fund grants 059113/z/99/a and 059113/z/99/z, and by Italian Ministry of Research (MIUR) grant no. 60470.

^* Address correspondence to G. Thomas Strickland, M.D., Ph.D, D.C.M.T., International Health Division, University of Maryland School of Medicine, 660 West Redwood Street, Suite 100, Howard Hall, Baltimore, Maryland 21201. E-mail: tstrick{at}epi.umaryland.edu

Authors’ addresses: Maged Al-Sherbiny, Ahmed Osman, and Nahla Mohamed, Department of Zoology, Cairo University Faculty of Science, 7 Okba Ebn Nafaa Dokki, Giza, Egypt, Telephone: (202) 336-2639, Fax: (202) 760-7146. Mohamed Tarek Shata, Viral Immunology Laboratory Hepatology Research Group, Division of Digestive Diseases, University of Cincinnati College of Medicine, 231 Albert B. Sabin Way, MSB 6360, Cincinnati, OH 45267-0595, Telephone: (513) 558-6110, Fax: (513) 558-1744. Fatma Abdel-Aziz, Center for Field and Applied Research, Ministry of Health and Population Warak, Giza, Egypt, Telephone: (202) 541-9403, Fax: (202) 540-5129. Mohamed Abdel-Hamid and Sayed F. Abdelwahab, Department of Microbiology and Immunology, Minya University Faculty of Medicine, Minya 61111, Egypt, Telephone: (20-86) 233-8180, Fax: (20-86) 234-2601. Nabiel Mikhail, South Egypt Cancer Institute Assuit University, Assuit, Egypt, Telephone: (20-12) 216-9517, Fax: (20-88) 333-342. Sonia Stoszek, International Health Division, Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, 660 W. Redwood Street, Suite 100, Howard Hall, Baltimore, MD 21210, Telephone: (410) 706-3467, Fax: (410) 706-8013. Lionello Ruggeri, Antonella Folgori, and Alfred Nicosia, Istituto di Ricerche di Biologia Molecolare-IRBM, via Pontina km 30600, 00040 Pomezia (Rome), Italy, Telephone: (39 06) 910-93327, Fax: (39 06) 910-93225. Alfred M. Prince, M.D., Head, Laboratory of Virology, Lindsley F. Kimball Research Institute of The New York Blood Center, 310 East 67th Street, New York, NY 10021, Telephone: (212) 570-3279, Fax: (212) 570-3180. G. Thomas Strickland, International Health Division, University of Maryland School of Medicine, 660 West Redwood Street, Suite 100, Howard Hall, Baltimore, MD 21201. E-mail: tstrick{at}epi.umaryland.edu.

Reprint requests: G. Thomas Strickland, M.D., Ph.D, D.C.M.T., International Health Division, University of Maryland School of Medicine, 660 West Redwood Street, Suite 100, Howard Hall, Baltimore, MD 21201, Telephone: (410) 706-7550, Fax: (410) 706-8013.

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