Journal
JOURNAL OF HEPATOLOGY
Volume 53, Issue 1, Pages 25-35Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jhep.2010.02.024
Keywords
Hepatitis C virus (HCV); Regulatory T cells; FoxP3; Immunohistochemistry; T lymphocytes; Liver
Categories
Funding
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Agence Nationale pour la Recherche sur le Sida (ANRS)
- Centre National de la Recherche Scientifique (CNRS)
- Higher Education Commission (HEC) of Pakistan
- Region-Rhone Alpes
- French government
- ANRS
Ask authors/readers for more resources
Background & Aims: In chronic hepatitis C (CHC), HCV-specific T-cell responses are often dysfunctionnal. In vitro data point out that regulatory T cells (Treg) are able to suppress HCV-specific lymphocyte proliferation and cytokine secretion but their implication in this pathology is still debated. Methods: Three complementary approaches were performed to investigate phenotype, frequency or localization of intra-hepatic Treg in treatment naive CHC patients. Double immunohistochemical analysis was performed in 20 formalin-fixed biopsies with CD8/FoxP3 and CD4/FoxP3 antibodies. Cellular markers and cytokines were investigated by quantitative RT-PCR in 27 additional frozen biopsies. Eight other fresh liver biopsies were selected for complementary analysis of immunophenotyping and frequency of intra-hepatic Treg. Results: Immunohistochemical analyses showed the presence of intra-hepatic CD4(+)FoxP3(+)T cells while CD8(+)FoxP3(+)T cells were very scarce. CD4(+)FoxP3(+)T cells were located in necro-inflammatory areas in contact with CD8(+)T cells, suggesting that Treg-mediated inhibition of CD8(+)T cell proliferation may occur by cell cell contact. RT-PCR analyses showed strong correlations between CD8, FoxP3, and IL-10 with emergence of four distinct gene clusters, CD8-FoxP3, CD8-IL-10, TGF-beta-IL-10, and TNF-alpha-TGF-beta. No correlation was found between serum viral load and any immune markers. Interestingly, the FoxP3(+)/CD8(+) cells ratio significantly decreased in severe fibrosis (F > 3) due to the dramatic decline of FoxP3 cells. Conclusions: This study provides new insights into the histological localization of Treg within HCV-infected liver, with a special accumulation of CD4(+)FoxP3(+)Treg cells in necro-inflammatory
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available