Characteristics of regulatory T-cell function in patients with chronic hepatitis B and C coinfection.

Regulatory T cells (Tregs) affect the pathogenesis and disease progression of chronic viral hepatitis. This study evaluated the frequency and function of Tregs in patients with chronic HBV/HCV coinfection. Seventy-four untreated HBV/HCV co-infected patients were enrolled in this study. These subjects were divided into four subgroups: HBV-active/HCV-active (BACA), HBV-inactive/HCV-active (BICA), HBV-active/HCV-inactive (BACI) and HBV-inactive/HCV-inactive (BICI). Treg frequency was calculated as the fraction of CD4+ Foxp3+ T cells among CD4+ T cells. Treg-mediated inhibition was measured as percent of inhibition of T-cell proliferation. The expression of interferon (IFN)-γ, tumour necrosis factor (TNF)-α and interleukin (IL)-10 with/without Treg inhibition was also studied. Among the patients, there were 8 cases of BACA (10.8%), 38 of BICA (51.4%), 14 of BACI (18.9%) and 14 of BICI (18.9%). The frequency of CD4+ Foxp3+ T cells was comparable between the four groups. The inhibitory function of Tregs among the patients in the BACA and BICA was higher than that in the BICI (BACA vs BICI, P = .0210; BICA vs BICI, P = .0301). Patients in the BACA and BICA had higher fibrosis-4 (FIB-4) scores and serum ALT levels and lower serum albumin levels than those of the other groups. ALT abnormality was significantly and independently associated with a higher Treg immunosuppressive ability. The IFN-γ expression of the effector T cells in the BACA was higher than that of the other groups. In conclusion, the inhibitory function of Tregs is higher among the HBV/HCV co-infected patients with active HCV infection. ALT abnormality plays a dominant role in Treg function.

Regulatory T Cell Function Modulated After Successful Direct-Acting Antiviral Treatment for Chronic Hepatitis C Patients.

BACKGROUNDS: Regulatory T cells (Tregs) affect the pathogenesis of chronic hepatitis C (CHC) infection. AIMS: This study evaluated the function of Tregs in CHC patients receiving the standard direct-acting antiviral agents (DAA) treatment. METHODS: CHC patients (n = 20) who received DAA treatment, clinical data, and function of Tregs were checked at baseline, Week 4, end of treatment (EOT), and 12 weeks after EOT (SVR 12). Treg-mediated inhibition was measured. The cytokine expression and fold change of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-10, and transforming growth factor (TGF)-ß with/without Treg inhibition were also detected. RESULTS: The cohort included 14 females with a mean age of 59.8 ± 11.5 years. Nineteen had HCV genotype 1. The HCV RNA level was 6.17 ± 0.70 log IU/mL. All patients reached the sustained virologic response. The frequency of CD4+Foxp3+T cells decreased from baseline to EOT and returned at SVR 12. The inhibitory function of Tregs decreased during treatment and then restored (baseline vs. EOT, P = 0.0393; EOT vs. SVR 12, P = 0.0052). The cytokine expression and fold change of IFN-γ and TNF-α were highest at EOT and then decreased at SVR 12. The fold change of IL-10 was lowest at EOT and then increased at SVR 12. The fold change of TGF-ß was significantly increased at Week 4 and SVR 12 compared to baseline. CONCLUSIONS: The frequency and inhibitory function of Tregs declined gradually from baseline to EOT and then increased from EOT to SVR 12 in CHC patients receiving DAA therapy. The expression of IFN-γ, TNF-α, IL-10, and TGF-ß parallelled Treg function.

Decrease in regulatory T-cell function in chronic hepatitis C patients receiving pegylated-interferon plus ribavirin.

OBJECTIVES: Regulatory T-cells (Tregs) play an important role in the pathogenesis of chronic hepatitis C (CHC) infection. Pegylated interferon is the standard therapy for CHC patients in Asian countries. This study aimed to evaluate the frequency and function of Tregs in CHC patients receiving combination therapy. METHODS: CHC patients (n=30) who had elevated alanine aminotransferase and underwent combination therapy were included. Clinical data and Treg function were checked at baseline, 12 weeks after treatment, at the end of treatment, and at the end of 24 weeks of follow-up. Treg immunosuppressive activity was measured as the inhibition ratio of conventional T-cell proliferation. RESULTS: Treg-mediated immunosuppression was significantly lower during therapy than at baseline (baseline 44.45%; 12 weeks 18.41% (p=0.042); end of treatment 22.62% (p=0.036); end of follow-up 17.46% (p=0.003)). Treg-mediated immunosuppression was higher in patients with a sustained virological response (SVR) than in those without SVR at the end of follow-up (SVR 24.20%, non-SVR 6.87%; p=0.030). CONCLUSION: Treg-mediated immunosuppression was lower during and after combination therapy, regardless of the treatment response, and higher in patients with SVR than in those without SVR at the end of follow-up.

Elevated frequency and function of regulatory T cells in patients with active chronic hepatitis C.

BACKGROUND: Regulatory T cells (Tregs) play a pivotal role in the persistence of hepatitis C virus infection. The aim of this study was to evaluate the frequency and function of Tregs in patients with chronic hepatitis C (CHC). METHODS: We enrolled 44 CHC patients with elevated alanine aminotransferase (ALT) levels (CH group), 13 CHC patients with persistent normal ALT levels (PNALT group), and 14 age-matched healthy subjects (HS group; controls). Tregs were identified as CD4+, CD25+, and forkhead box P3 (Foxp3)+ T lymphocytes, using three-color fluorescence-activated cell sorting (FACS). The frequency of Tregs was determined by calculating the percentage of CD4+CD25(high) T cells among CD4 T cells. CD127 and CD45RA were also analyzed for subsets of Tregs. The levels of serum transforming growth factor (TGF)-ß and interleukin (IL)-10 in immunosuppressive assays were detected by enzyme-linked immunosorbent assay (ELISA). The immunosuppressive abilities of Tregs were evaluated by measuring their ability to inhibit the proliferation of effector cells. RESULTS: Higher proportions of Tregs were found in the CH and PNALT groups compared with the HS group. The populations of CD127 low/negative and CD45RA negative cells were higher in the CH group than in the PNALT group. The expressions of IL-10 and TGF-ß in the CH and PNALT groups were significantly higher than those in the HS group. In addition, the immunosuppressive ability of Tregs from the CH group was increased relative to that in the PNALT and the HS group. CONCLUSIONS: CHC patients, irrespective of liver function, had higher frequencies of Tregs than healthy subjects; however, only CHC patients with inflammation showed enhanced immunosuppressive function of Tregs.

Dysfunction of natural killer cells in patients with transitional cell carcinoma.

Previous studies had established that transforming growth factor-beta1 (TGF-beta1) is highly expressed in bladder tumor, facilitating progression and spreading of the cancerous cells. Here, we report that both the number and the cytotoxic function of natural killer (NK) cells are decreased in patients with superficial transitional cell carcinoma (TCC). In consistent with previously reported findings, the plasma TGF-beta1 concentration is also elevated in patients with superficial TCC. In vitro, the cytotoxic function of NK cells was impaired by the presence of TGF-beta1. Hence, our data suggested elevated concentration of serum TGF-beta1 in loss of NK cytotoxicity in superficial TCC patients, implicating altered innate immunity may correlate with the incidence of TCC.