Interleukin (IL)-17/IL-22-Producing T cells Enriched Within the Liver of Patients with Chronic Hepatitis C Viral (HCV) Infection
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Effector CD4+ helper T cells have historically been classified into T helper 1 (Th1) and Th2 based on the production of signature cytokines. The recently identified interleukin (IL)-17 cytokine family plays important roles in host immunity against intracellular pathogens and in chronic inflammatory conditions; data have implicated IL-17 in autoimmune and viral liver disease.
This study used three patient groups with HCV infection: acute HCV who either cleared spontaneously or became chronically infected (n = 12), endstage liver disease from whom both peripheral and intrahepatic lymphocytes were studied directly ex vivo (n = 11), and 134 patients with different stages of HCV-related fibrosis from whom serum was collected concurrently with liver biopsy. Normal healthy subjects (n = 41) served as controls.
Acute HCV was not associated with expansion of either CD4+ or CD8+ T cells producing IL-17 (Th17, Tc17) or IL-22, and frequencies did not differ in the blood of patients who cleared versus became persistently infected. The hepatic compartment of chronic HCV patients demonstrated statistically more CD4+ and CD8+ that produced IL-17, IL-22 or both as compared to peripheral blood. These T cells displayed a distinct phenotypic profile, high expression of the homing receptor CD161 and low levels of inhibitory receptors, mucin-domain-containing-molecule-3 (Tim-3) and programmed-death 1. Using a sensitive ELISA, we found no significant differences in serum levels of IL-17 according to HCV-related fibrosis.
In chronic HCV, T cells producing IL-17/IL-22 may home to the liver; however, circulating levels of IL-17 do not correlate with fibrosis.
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- Interleukin (IL)-17/IL-22-Producing T cells Enriched Within the Liver of Patients with Chronic Hepatitis C Viral (HCV) Infection
Digestive Diseases and Sciences
Volume 57, Issue 2 , pp 381-389
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- 1. Division of Gastroenterology and Hepatology, Hepatitis C Center, Department of Medicine, University of Colorado Denver and National Jewish Hospital, B-158, Academic Office Building 1, 12631 E. 17th Ave., Rm. 7614, P.O. Box 6511, Aurora, CO, 80045, USA
- 2. Integrated Program in Immunology, University of Colorado Denver and National Jewish Hospital, Denver, CO, USA
- 4. Eastern Colorado VA, Denver, CO, USA
- 3. Denver VA Medical Center, Denver, CO, USA