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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Pharmacy, Duksung Women's University College of Pharmacy, Seoul, Korea.
Hyosun
H
Cho
Department of Pharmacy, Kyungpook National University College of Pharmacy, Daegu, Korea.
Hyojeung
H
Kang
Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea.
Chang Wook
CW
Kim
Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea.
Hee Yeon
HY
Kim
Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea.
Jeong Won
JW
Jang
Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea.
Seung Kew
SK
Yoon
Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea.
Chang Don
CD
Lee
D000208:Acute Disease; D000328:Adult; D060908:CTLA-4 Antigen / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D006505:Hepatitis / Q000235:genetics; D006506:Hepatitis A / Q000235:genetics* / Q000821:virology; D017957:Hepatitis A Virus, Human; D006801:Humans; D008297:Male; D010641:Phenotype; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics*; D013601:T-Lymphocytes / Q000378:metabolism
D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
Acute hepatitis A; Cytotoxic T lymphocyte-associated antigen 4; Programmed death 1