Characterization of virus-specific T-cell immunity in liver allograft recipients with HCV-induced cirrhosis

Abstract

Recurrent hepatitis C infection (HCV) following liver transplantation causes accelerated allograft cirrhosis. Here we characterized HCV-specific immunity in adult liver transplant recipients (n = 74) with and without allograft cirrhosis. Patients were divided into hepatic inflammation/no cirrhosis (METAVIR scores 0-2, HIN) and hepatic cirrhosis (score 3-4, HFC). As control, 20 normal subjects and 10 non-HCV liver transplant patients were included. Twenty-five different serum cytokines were analyzed using LUMINEX. Frequency of T-cells specific to HCV-derived proteins (NS3, NS4, NS5, Core) was characterized using ELISPOT immunoassays. There was no difference in clinical characteristics between HIN (n = 49) and HFC (n = 25) groups. HIN group had high serum IFN-gamma and IL-12 while HFC demonstrated elevated IL-4, IL-5 and IL-10 (p < 0.01). HCV (NS3, NS4, NS5, Core)-specific IFN-gamma-producing CD4+ T-cells were elevated in the HIN group whereas the HFC patients showed predominance of HCV-specific IL-5 and IL-10-producing CD4+ T-cells.

Conclusions: Lack of HCV-specific Th1-type T-cell immunity is observed in liver transplant recipients with advanced allograft cirrhosis.

Figure 1. Lack of HCV-specific IFN-γ producing T lymphocytes in OLT recipients with HCV-induced allograft cirrhosis

The frequency of peripheral blood T lymphocytes specific to HCV derived proteins, NS3, NS4, NS5 and core was determined by means of IFN-γ ELISPOT assay. The data is representative of all experiments done in triplicate and the standard error bars are demonstrated. Patients with hepatic inflammation (HIN, n=49, white bars) demonstrated significantly higher frequency of IFN-γ producing HCV-specific T lymphocytes compared to patients with hepatic fibrosis (HFC, n=25, black bars) and healthy control individuals (n=20, grey bars, p<0.05). The frequency of T lymphocytes reactive to the mumps antigen was comparable.

Figure 2. High frequency of HCV-specific IL-5 producing T lymphocytes in OLT recipients with HCV-induced allograft cirrhosis

The frequency of peripheral blood T lymphocytes specific to HCV derived proteins, NS3, NS4, NS5 and core was determined by means of IL-5 ELISPOT assay. The data is representative of all experiments done in triplicate and the standard error bars are demonstrated. Patients with hepatic fibrosis (HFC, n=25, black bars) demonstrated significantly higher frequency of IL-5 producing HCV-specific T lymphocytes compared to patients with hepatic inflammation (HIN, n=49, white bars) and healthy control individuals (n=20, grey bars, p<0.05). The frequency of T lymphocytes reactive to the mumps antigen was comparable.

Figure 3. High frequency of HCV-specific IL-10 producing T lymphocytes in OLT recipients with HCV-induced allograft cirrhosis

The frequency of peripheral blood T lymphocytes specific to HCV derived proteins, NS3, NS4, NS5 and core was determined by means of IL-10 ELISPOT assay. The data is representative of all experiments done in triplicate and the standard error bars are demonstrated. Patients with hepatic fibrosis (HFC, n=25, black bars) demonstrated significantly higher frequency of IL-10 producing HCV-specific T lymphocytes compared to patients with hepatic inflammation (HIN, n=49, white bars) and healthy control individuals (n=20, grey bars, p<0.05). The frequency of T lymphocytes reactive to the mumps antigen was comparable.