Characterization and role of intra-hepatic regulatory T cells in chronic hepatitis C pathogenesis

Stürm, Nathalie; Thélu, M.A.; Camous, Xavier; Dimitrov, Guéorgui; Ramzan, Muhammad; Dufeu‐Duchesne, Tania; Bonorino, Paula; Guillermet, Christiane; Brambilla, Élisabeth; Arvers, Philippe; Pernollet, Martine; Leroy, Vincent; Zarski, Jean–Pierre; Marche, Patrice N.; Jouvin‐Marche, Evelyne

doi:10.1016/j.jhep.2010.02.024

Cited by 56 publications

(61 citation statements)

References 51 publications

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“…T reg plays a fundamental role in maintaining immune homeostasis and the balance between the tissue-damaging and protective effects of the immune response (Cabrera et al, 2004;Keynan et al, 2008;Sturm et al, 2010). In a previous study by our laboratory (Hetta et al, 2015), we reported that the frequency of colonic T reg in HCV-infected patients was higher than those in the controls.…”

Section: Discussionmentioning

confidence: 92%

Extra-hepatic infection of hepatitis C virus in the colon tissue and its relationship with hepatitis C virus pathogenesis

Hetta

Mekky

Khalil

et al. 2016

Journal of Medical Microbiology

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Extra-hepatic compartments might contribute to hepatitis C virus (HCV) persistence and extrahepatic manifestations. Therefore, we investigated HCV infection in colonic tissue in patients with chronic hepatitis C (CHC) and its relationship with HCV pathogenesis. Colonic biopsies were collected from three groups with CHC infection: treatment naïve (TN; n=12), non-responders (NR; n=10) to anti-HCV therapy (pegylated interferon-a and ribavirin) and sustained virologic response (SVR; n=10) and from a fourth healthy control group (n=10). Liver biopsies were examined to assess inflammation and fibrosis. HCV infection and colonic T regulatory (T reg ) frequency were detected by immunohistochemistry. HCV core and NS3 proteins were detected in B cells and macrophage/monocytes of 42 % and 25 % of TN and 50 % and 30 % of NR, respectively, but not in SVR or control group. The numbers of cells expressing HCV proteins were positively correlated with both HCV viral load and colonic T reg frequency. A significant negative correlation between HCV-expressing cells with both liver inflammation and fibrosis was identified. Our study provides evidence that HCV can infect B cells and macrophages of the colon. The correlations between HCV infection in colonic tissue and HCV viral load and liver pathology underline the significance of this extra-hepatic infection in HCV pathogenesis and response to therapy.

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Section: Discussionmentioning

confidence: 92%

Extra-hepatic infection of hepatitis C virus in the colon tissue and its relationship with hepatitis C virus pathogenesis

Hetta

Mekky

Khalil

et al. 2016

Journal of Medical Microbiology

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“…Recently, Sturm [57] revealed that Tregs are in contact with CD8? T cells in necroinflammatory areas of liver tissues with chronic hepatitis.…”

Section: Regulatory T Cellsmentioning

confidence: 99%

Different aspects of CD4 T cells that lead to viral clearance or persistence of HCV infection

Sugimoto

Shiraki

2011

Hepatol Int

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More than 170 million people worldwide are infected with hepatitis C virus (HCV). A characteristic of this virus is a high tendency toward chronic infection. Several factors affect the viral outcome after infection. Among them, HCV-specific CD4 T cells are thought to play a crucial role in controlling viremia. Cumulative data showed that spontaneously resolved individuals have vigorous CD4 T-cell responses to a broad spectrum of HCV antigens and maintain these responses over a long period of time, whereas chronically infected patients lose their CD4 T-cell responses in the acute phase of infection. Although several possibilities of why CD4 T cells lose their function have been proposed, the mechanisms are not completely understood. Moreover, there is another subset of CD4 T cells called regulatory T cells (Tregs). These cells suppress immune reaction of T cells, B cells, and antigen-presenting cells, and are thought to protect organs from immune overreaction and autoimmunity. An increasing amount of data supports the possibility that Tregs participate in the mechanism of HCV persistence. It is obvious that CD4 T cells are the main effectors controlling HCV outcome. To achieve a better prognosis, we need to understand the mechanism of how HCV earns its chronicity by escaping from host cellular immune attacks. In this review, we will focus on the role of HCV-specific T cells in controlling viremia, particularly the aspects of these cells being either inhibitors or propellers of chronic infection.

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“…Moreover, patients with high viral load have a higher proportion of Tregs in the liver (Stoop et al, 2008), suggesting that intrahepatic Tregs suppress antiviral immune responses in the liver in chronic hepatitis B virus infection. In HCV infection, it has also been shown that a higher frequency of CD4 + CD25 + regulatory T cells in the blood of chronically HCV-infected patients versus recovered or healthy individuals (Cabrera et al, 2004;Boettler et al, 2005) and the presence of CD4 + FoxP3 + T cells in the liver of chronically HCV-infected patients (Sturm et al, 2010).…”

Section: Regulatory T Cells (Tregs)mentioning

confidence: 99%

Immunopathogenesis and Immunotherapy for Viral Hepatitis

Shimizu¹

2011

Viral Hepatitis - Selected Issues of Pathogenesis and Diagnostics

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Characterization and role of intra-hepatic regulatory T cells in chronic hepatitis C pathogenesis

Cited by 56 publications

References 51 publications

Extra-hepatic infection of hepatitis C virus in the colon tissue and its relationship with hepatitis C virus pathogenesis

Extra-hepatic infection of hepatitis C virus in the colon tissue and its relationship with hepatitis C virus pathogenesis

Different aspects of CD4 T cells that lead to viral clearance or persistence of HCV infection

Immunopathogenesis and Immunotherapy for Viral Hepatitis

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