Phenotypic Characteristics of PD-1 and CTLA-4 Expression in Symptomatic Acute Hepatitis A

• Published in: Gut and liver Vol. 10; no. 2; pp. 288 - 294
• Main Authors: Cho, Hyosun, Kang, Hyojeung, Kim, Chang Wook, Kim, Hee Yeon, Jang, Jeong Won, Yoon, Seung Kew, Lee, Chang Don
• Format: Journal Article
• Language: English
• Published: Korea (South) Editorial Office of Gut and Liver 01.03.2016; Gastroenterology Council for Gut and Liver; 거트앤리버 소화기연관학회협의회
• Subjects: Acute Disease; acute hepatitis a; Adult; Case-Control Studies; CTLA-4 Antigen - genetics; cytotoxic t lymphocyte-associated antigen 4; Female; Flow Cytometry; Hepatitis - genetics; Hepatitis A - genetics; Hepatitis A - virology; Hepatitis A Virus, Human; Humans; Male; Original; Phenotype; Programmed Cell Death 1 Receptor - genetics; programmed death 1; T-Lymphocytes - metabolism; 내과학; Cytotoxic T lymphocyte-associated antigen 4; Programmed death 1; Acute hepatitis A
• ISSN: 1976-2283; 2005-1212
• DOI: 10.5009/gnl14368

The immunoregulatory molecules programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are associated with the dysfunction of antiviral effector T-cells, which leads to T-cell exhaustion and persistent viral infection in patients with chronic hepatitis C and chronic hepatitis B. Little is known about the role of PD-1 and CTLA-4 in patients with symptomatic acute hepatitis A (AHA). Peripheral blood mononuclear cells were isolated from seven patients with AHA and from six patients with nonviral acute toxic hepatitis (ATH) during the symptomatic and convalescent phases of the respective diseases; five healthy subjects acted as controls. The expression of PD-1 and CTLA-4 on T-cells was measured by flow cytometry. PD-1 and CTLA-4 expression during the symptomatic phase was significantly higher in the T-cells of AHA patients than in those of ATH patients or healthy controls (PD-1 18.3% vs 3.7% vs 1.6%, respectively, p<0.05; CTLA-4 23.5% vs 6.1% vs 5.9%, respectively, p<0.05). The levels of both molecules decreased dramatically during the convalescent phase of AHA, whereas a similar pattern was not seen in ATH. Our findings are consistent with a viral-protective effect of PD-1 and CTLA-4 as inhibitory molecules that suppress cytotoxic T-cells and thereby prevent the destruction of virus-infected hepatocytes in AHA.