Digestive Diseases and Sciences

, Volume 57, Issue 2, pp 381–389 | Cite as

Interleukin (IL)-17/IL-22-Producing T cells Enriched Within the Liver of Patients with Chronic Hepatitis C Viral (HCV) Infection

  • Richard G. Foster
  • Lucy Golden-Mason
  • Alleluiah Rutebemberwa
  • Hugo R. Rosen
Original Article

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Keywords

HCV Liver Th17 IL22 Fibrosis 

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Richard G. Foster
    • 1
  • Lucy Golden-Mason
    • 1
    • 2
    • 4
  • Alleluiah Rutebemberwa
    • 1
  • Hugo R. Rosen
    • 1
    • 2
    • 3
    • 4
  1. 1.Division of Gastroenterology and Hepatology, Hepatitis C Center, Department of MedicineUniversity of Colorado Denver and National Jewish HospitalAuroraUSA
  2. 2.Integrated Program in ImmunologyUniversity of Colorado Denver and National Jewish HospitalDenverUSA
  3. 3.Denver VA Medical CenterDenverUSA
  4. 4.Eastern Colorado VADenverUSA

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