Evaluation of circulating CD4+CD25+ and liver-infiltrating Foxp3+ cells in HCV-associated liver disease

Amoroso, A; D'Amico, Fabio; Consolo, M; Skarmoutsou, Evangelia; Neri, Sergio; Dianzani, Umberto; Spandidos, Demetrios Α.; Mazzarino, María Clorinda

doi:10.3892/ijmm.2012.947

Cited by 5 publications

(5 citation statements)

References 16 publications

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“…Recent data from our laboratory have suggested that colonic T reg cells are negatively correlated with liver inflammation and HCV viral load, which supports a strong linkage between gut-derived T reg and HCV infection [35, 36]. T reg cells appear to assist in the maintenance of chronicity by inhibition of anti-HCV immune responses and consequently attenuate the intrahepatic tissue-damaging response to infection [26, 32]. …”

Section: Introductionmentioning

confidence: 87%

“…In cases of chronic hepatitis C (CHC), there is evidence that the frequency of T reg cells is higher than in controls and is negatively correlated with the necro-inflammatory score [29–31]. The elevated frequency of T reg cells may explain the weak HCV-specific T-cell responses in CHC [32]. Moreover, there is some evidence that individuals with CHC may harbour more T reg cells in their peripheral circulation [33] and in the liver than those uninfected [34].…”

Section: Introductionmentioning

confidence: 99%

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Association between IL28B rs12979860 single nucleotide polymorphism and the frequency of colonic Treg in chronically HCV-infected patients

et al. 2016

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The IL28B gene is associated with spontaneous or treatment-induced HCV viral clearance. However, the mechanism by which the IL28B single nucleotide polymorphism (SNP) affects the extra-hepatic HCV immune responses and its relationship to HCV pathogenesis have not been thoroughly investigated. To examine the mechanism by which IL28B affects HCV clearance. Forty Egyptian patients with chronic HCV infection receiving an Interferon/ribavirin treatment regimen were enrolled into this study. There were two groups: non-responders (NR; n = 20) and sustained virologic responders (SVR; n = 20). The initial plasma HCV viral loads prior to treatment and IL28B genotypes were determined by quantitative RT-PCR and sequencing, respectively. Liver biopsies were examined to determine the inflammatory score and the stage of fibrosis. Colonic regulatory T cell (Treg) frequency was estimated by immunohistochemistry. No significant association between IL28B genotypes and response to therapy was identified, despite an odds ratio of 3.4 to have the TT genotype in NR compared to SVR (95 % confidence interval 0.3–35.3, p = 0.3). Patients with the TT-IL28Brs12979860 genotype (unfavorable genotype) have significantly higher frequencies of colonic Treg compared to the CT (p = 0.04) and CC (p = 0.03) genotypes. The frequency of colonic Treg cells in HCV-infected patients had a strong association with the IL-28B genotype and may have a significant impact on HCV clearance.

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Section: Introductionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Association between IL28B rs12979860 single nucleotide polymorphism and the frequency of colonic Treg in chronically HCV-infected patients

et al. 2016

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“…Chronic HCV cases have an increased frequency of T reg cells compared to controls and the T reg cells negatively correlated with the degree of inflammation [ 76 – 78 ]. The higher frequency of T reg cells may also explain the weak HCV-specific T-cell responses in chronic HCV patients [ 79 ]. There is also some evidence that chronic HCV patients may harbour more T reg cells in their peripheral circulation [ 80 ] and in the liver than those who are uninfected [ 81 ].…”

Section: Reviewmentioning

confidence: 99%

“…There is also some evidence that chronic HCV patients may harbour more T reg cells in their peripheral circulation [ 80 ] and in the liver than those who are uninfected [ 81 ]. Thus, T reg cells appear to assist in the maintenance of chronic infection by inhibiting anti-HCV responses and, therefore, attenuating the intrahepatic tissue-damaging response to infection [ 79 , 82 ].…”

Section: Reviewmentioning

confidence: 99%

Cellular immune response to hepatitis-C-virus in subjects without viremia or seroconversion: is it important?

Abdelwahab

2016

Infect Agents Cancer

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Hepatitis C Virus (HCV) causes chronic infection and represents a global health burden. To date, there is no licensed vaccine for HCV. The high viral replication rate and the existence of several HCV genotypes and quasispecies hamper the development of an effective universal vaccine. In this regard, the current HCV vaccine candidates show genotype-specific protection or narrow cross reactivity against other genotypes. Importantly, HCV spontaneous clearance occurs in 15–50 % of infected subjects, indicating that natural resistance to chronic infection exists. This phenomenon was demonstrated among humans and chimpanzees and continues to motivate researchers attempting to develop an effective HCV vaccine. However, what constitutes a protective immune response or correlate of protection against HCV infection is still vague. Additionally, the mechanisms behind successful HCV clearance suggest the coordination of several arms of the immune system, with cell-mediated immunity (CMI) playing a crucial role in this process. By contrast, although neutralizing antibodies have been identified, they are isolate-specific and poorly correlate with viral clearance. Antigen-specific CD4 T cells, instead, correlate with transient decline in HCV viremia and long-lasting control of the infection. Unfortunately, HCV has been very successful in evading host immune mechanisms, leading to complications such as liver fibrosis, cirrhosis and hepatocellular carcinoma. Interestingly, CMI to HCV antigens were shown among exposed individuals without viremia or seroconversion, suggesting the clearance of prior HCV infection(s). These individuals include family members living with HCV-infected subjects, healthcare workers, IV drug users, and sexual contacts. The correlates of protection could be closely monitored among these individuals. This review provides a summary of HCV-specific immune responses in general and of CMI in particular in these cohorts. The importance of these CMI responses are discussed.

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“…(Fiore et al 1997; Koziel and Walker 1997). T-regulatory cells were extensively studied by various groups and considered to be involved in the induction of tolerance to viral antigens in affected hosts (Amoroso et al 2012; Miyaaki et al 2009). On the contrary, NK cells were found to be suppressed by HCV proteins (Cheent and Khakoo 2011; Varchetta et al 2012; Wen et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Detection and Significance of Cytotoxic Cell Subsets in Biopsies of HCV-Infected Human Livers

Mozer‐Lisewska¹,

Mania²,

Kowala‐Piaskowska³

et al. 2013

Arch. Immunol. Ther. Exp.

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Chronic viral hepatitis C still remains the clinical challenge. Attempts of the immune system to cope with this infection are unsatisfactory. There is a conviction that the main site of interaction between virus (Hepatitis C virus, HCV) and immune system is in situ, i.e., in liver. Natural killer (NK) cells appeared relevant in the acute hepatitis. Less is known about the immune response in the chronic HCV infection. The aim of this study was to evaluate the prevalence of various cytotoxic cell subsets in chronic HCV+ liver tissue and to seek links between them and laboratory data of patients. Sections from paraffin blocks of liver biopsy tissues of HCV+ untreated patients were subjected to the reaction with antibodies vs. cytotoxic cell subsets and immunohistochemistry. Positive cells were searched in cellular infiltrates in portal areas and in liver parenchyma. They were classified on the “Yes” or “No” basis. Majority of liver biopsies exhibited cellular infiltrates in portal spaces and as single cells in liver parenchyma. Infiltrates consisted of CD8+ T cells, CD56+ NK ones, including CD158i+ and CD158b+. The latter were rarely seen. There were also granzyme B+ cells. The most abundant were NKG2D+ cells, much more common than NK CD56+ ones. It implied that NKG2D was also expressed on T cells. Prevalence of NKG2D+ cells correlated with high activity of liver enzymes such as alanine aminotransferase, aspartate aminotransferase and a greater histological severity of liver injury. NKG2D+ cells form the bulk of cells infiltrating HCV-infected human liver. Correlation of NKG2D+ cells with some laboratory parameters of patients suggests their role in hepatitis C pathogenesis.

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Evaluation of circulating CD4+CD25+ and liver-infiltrating Foxp3+ cells in HCV-associated liver disease

Cited by 5 publications

References 16 publications

Association between IL28B rs12979860 single nucleotide polymorphism and the frequency of colonic Treg in chronically HCV-infected patients

Association between IL28B rs12979860 single nucleotide polymorphism and the frequency of colonic Treg in chronically HCV-infected patients

Cellular immune response to hepatitis-C-virus in subjects without viremia or seroconversion: is it important?

Detection and Significance of Cytotoxic Cell Subsets in Biopsies of HCV-Infected Human Livers

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