Abstract
Hepatitis C virus infection is a major cause of chronic liver disease. CD4+ T cells play a key role in disease outcome. However, the critical functions and associated phenotypes of intrahepatic CD4+ T cells are not well defined. We have previously shown that CD8+T cells expressing the C type lectin CD161 are highly enriched in the human liver, especially during chronic hepatitis. These cells are associated with a type 17 differentiation pattern and express cytokines including IL-17A, IL-22, and IFN-γ. We therefore analyzed expression of CD161 on CD4+ T cells in blood and liver and addressed the relevant phenotype and functional capacity of these populations. We observed marked enrichmentof CD161+ CD4+ T cells in the liver during chronic hepatitis such that they are the dominant subtype (mean 55% of CD4+ T cells). IL-22 and IL-17 secreting CD4+ T cells were readily found in the livers of HCV and NASH donors, although not enriched compared to blood. There was, however, specific enrichment of a novel subset of IL-22/IFN-γ dual secretors (p = 0.02) compared to blood, a res+ult reconfirmed with direct ex vivo analyses. These data indicate the dominance of CD161+ expressing lymphocyte populations within the hepatic infiltrate, associated with a distinct cytokine profile. Given their documented roles as antiviral and hepatoprotective cytokines respectively, the impact of co-secretion of IFN-γ and IL-22 in the liver may be particularly significant.
Original language | English (US) |
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Article number | Article 346 |
Journal | Frontiers in immunology |
Volume | 3 |
Issue number | NOV |
DOIs | |
State | Published - 2012 |
Externally published | Yes |
Keywords
- CD161
- CD4 t cell
- HCV
- Hepatic inflammation
- IL-22
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology