Role of the Regulatory T lymphocytes in hepatitis C fibrosis progression

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Hepatitis C virus (HCV) becomes chronic in about 85 % of infected individuals, whereas only 15 % of infected people clear spontaneously the virus. The progression of hepatitis C to chronic status is associated to a profound down-regulation of CD4 and CD8 multispecific immune response. This immune defect may participate to the immune tolerance of VHC and consequently to its persistence. Recent findings indicate that T regulatory cells as Tr1 play an inhibitory role on T helper responses notably in the context of auto-immune or inflammatory disorders. The existence of immunosuppressive mechanisms supported by Tr1 lymphocytes and their IL-10 production represent an attractive hypothesis. We have previously evaluated the existence of regulatory T cells (Tr1) via high production of IL-10, in liver biopsies of three well-defined cohorts of HCV-1b infected patients. To this purpose, we compared liver biopsies of chronically infected patients including patients without liver lesions, with cirrhosis and with hepatocellular carcinoma (HCC). Using quantitative real time PCR, the results obtained demonstrate, an increased expression of interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta)_, in liver biopsies with more severe fibrosis. This observation was correlated with an increased expression during the pathogenesis progression, of the three specific markers of the Tr1 cells sub-population, recently described and confirming the Tr1 phenotype. Evidence of regulatory T cells installation in the liver of chronically infected patient and increased frequency in cirrhosis and HCC suggest a main role of these cells in the aggravation of the liver pathology. This study should bring insight of T regulatory cell implications in VHC persistence and in the pathology progression.