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Cutting Edge: Identification of Hepatitis C Virus-Specific CD8⁺ T Cells Restricted by Donor HLA Alleles following Liver Transplantation¹

Hugo R. Rosen^2,*,,, David J. Hinrichs^,, Rachel L. Leistikow, Glenda Callender^¶, Anne M. Wertheimer^,, Michael I. Nishimura^¶ and David M. Lewinsohn^,,

^* Hepatology and Liver Transplantation Program, Portland Veterans Affairs Medical Center/Oregon Health and Sciences University, Molecular Microbiology and Immunology, Oregon Health and Sciences University, Portland Veterans Affairs Medical Center Research Services, Division of Pulmonary and Critical Care, Portland Veterans Affairs Medical Center, Portland, OR 97207; and ^¶ Department of Surgery, University of Chicago, Chicago, IL 60637

By necessity, human liver transplantation is performed across HLA barriers. As a result, intracellular infection of the allograft presents a unique immunologic challenge for the recipient’s immune system. In this study, we describe the presence of HLA-A2-restricted, hepatitis C virus (HCV)-specific CD8⁺ T cells in liver transplant recipients in whom the allograft is HLA-A2 positive and the recipient is HLA-A2 negative. These memory-effector T cells are recipient derived and recognize HCV peptide uniquely in the context of HLA-A2. Furthermore, these cells were absent before the transplant, suggesting that the allograft is capable of selectively expanding naive CD8⁺ T cells. The in vitro specificity to donor HLA allele-restricted CD8⁺ T cells suggests that these cells may function to control HCV spread in the allograft.

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