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

• Published in: Hepatology (Baltimore, Md.) Vol. 44; no. 5; pp. 1098 - 1109
• Main Authors: Golden‐Mason, Lucy, Burton, James R., Castelblanco, Nicole, Klarquist, Jared, Benlloch, Salvador, Wang, Chia, Rosen, Hugo R.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.11.2006; Wiley
• Subjects: Acute Disease; Adult; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - physiology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - physiology; Epitopes; Female; Flow Cytometry; Hepacivirus - immunology; Hepatitis C - immunology; Hepatitis C, Chronic - immunology; Human viral diseases; Humans; Immunologic Memory; Infectious diseases; Interleukin-7 Receptor alpha Subunit - metabolism; Male; Medical sciences; Middle Aged; Phenotype; Prospective Studies; Receptors, Interleukin-7 - immunology; Receptors, Interleukin-7 - metabolism; RNA, Viral - isolation & purification; Viral diseases; Viral hepatitis; Infection; Persistence; Chain; Acute; Viral disease; Digestive diseases; Hepatic disease; Viral hepatitis C
• ISSN: 0270-9139; 1527-3350
• DOI: 10.1002/hep.21365

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.)