Loss of IL-7 receptor alpha-chain (CD127) expression in acute HCV infection associated with viral persistence

Authors

  • Lucy Golden-Mason,

    1. Division of Gastroenterology & Hepatology, Hepatitis C Center, and Integrated Program in Immunology, University of Colorado Health Sciences Center & National Jewish Hospital, Denver, CO
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  • James R. Burton Jr,

    1. Division of Gastroenterology & Hepatology, Hepatitis C Center, and Integrated Program in Immunology, University of Colorado Health Sciences Center & National Jewish Hospital, Denver, CO
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  • Nicole Castelblanco,

    1. Division of Gastroenterology & Hepatology, Hepatitis C Center, and Integrated Program in Immunology, University of Colorado Health Sciences Center & National Jewish Hospital, Denver, CO
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  • Jared Klarquist,

    1. Division of Gastroenterology & Hepatology, Hepatitis C Center, and Integrated Program in Immunology, University of Colorado Health Sciences Center & National Jewish Hospital, Denver, CO
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  • Salvador Benlloch,

    1. Hepatogastroenterology Department, Hospital Universitario La Fe, Valencia, Spain
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  • Chia Wang,

    1. Harborview Medical Center/University of Washington, Seattle, WA
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  • Hugo R. Rosen

    Corresponding author
    1. Division of Gastroenterology & Hepatology, Hepatitis C Center, and Integrated Program in Immunology, University of Colorado Health Sciences Center & National Jewish Hospital, Denver, CO
    • Division of Gastroenterology/Hepatology, University of Colorado Health Sciences Center GI Division, 4200 East Ninth Ave. #B-158, Denver, CO 80262
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    • fax: 303-315-5711.


  • Potential conflict of interest: Nothing to report.

Abstract

Interleukin-7 (IL-7) is required for the establishment and maintenance of memory CD4+ and CD8+ T lymphocytes, and cells lacking IL-7Rα (CD127) demonstrate impaired IL-2 secretion and have a short life-span. Chronic HCV is characterized by T cells that are functionally impaired and exhibit an immature phenotype. To investigate the potential role of IL-7/IL-7Rα in the outcome of HCV infection, we used multiparameter flow cytometry to characterize patients with acute infection (n = 24), long-term chronic infection (12) and normal subjects (13). HCV infection per se resulted in downregulation of CD127 on total CD4+ and CD8+ T lymphocytes as compared to normal controls. Total expression was lowest in those patients who subsequently developed persistence and intermediate in those patients with acute-resolving infection. This reduction affected both naïve and effector/memory T cells. CD127 correlated phenotypically with upregulation of chemokine receptors CCR7 and CXCR4, expression of the anti-apoptotic molecule B cell leukemia/lymphoma 2 (Bcl-2), and enhanced IL-2 production. In six HLA A2-positive patients, we longitudinally tracked tetramer responses to HCV and CMV epitopes; at baseline, reflecting the expression of CD127 on whole T cell populations, viral-specific CTLs in patients who became chronic demonstrated lower CD127. In conclusion, CD127 is a useful marker of functional CD4+ and CD8+ T cells and its expression correlates with virologic outcome of acute HCV. These data provide a mechanistic basis for the observation that CTLs generated in early infection rapidly decline as chronicity is established; CD127 expression should be considered in the design of novel immunotherapeutic approaches. (HEPATOLOGY 2006;44:1098–1109.)

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