Study of liver-targeted regulatory T cells in hepatitis B and C virus in chronically infected patients.
BACKGROUND
Regulatory T cells (Tregs) play a critical role in chronic viral infections. The role of Tregs in chronic hepatitis B (CHB) and chronic hepatitis C (CHC) is unknown. This study examined the distribution and frequency of forkhead box p3(+) (Foxp3(+)) Tregs in the liver tissue and compared the clinicopathological characteristics of CHB and CHC patients.


METHODS
Liver needle biopsies were obtained from 26 patients who were hepatitis B surface antigen positive and 27 patients who were hepatitis C virus antibody positive.


RESULTS
The ratio of Foxp3(+) Tregs in CD3(+) T cells was similar in HBV and in HCV cases. In HBV cases, the variables that were positively associated with the ratio of Foxp3(+) Tregs in CD3(+) T cells included the serum alanine aminotransferase level (R=0.402, P=0.025) and the ratio of CD8(+) T cell plus CD56(+) NK cell against CD4(+) T cell (R=0.53, P=0.005). The ratio of Foxp3(+) Tregs in CD3(+) T cells increased more in the severe activity group than in the mild activity group (P=0.04). In HCV cases, the ratio of Foxp3(+) Tregs in CD3(+) T cells increased significantly in terms of the genotype2 (P=0.0002) and male gender (P=0.04). In addition, the ratio of Foxp3(+) Tregs in CD3(+) T cells showed a negative correlation with the ratio of CD8(+) T cell plus CD56(+) NK cell against CD4(+) T cell (R=-0.508, P=0.005) and HCV viral load (R=-0.482, P=0.001).


CONCLUSIONS
Liver-targeted regulatory T cells present similarly in CHB and CHC, but their relationship with the effector cell population, the inflammation grade or the viral load is different between CHB and CHC.
Miyaaki
Hisamitsu
H
The First Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, Japan. miyaaki-hi@umin.ac.jp
Zhou
Huijuan
H
Ichikawa
Tatsuki
T
Nakao
Kazuhiko
K
Shibata
Hidetaka
H
Takeshita
Shigeyuki
S
Akiyama
Motohisa
M
Ozawa
Eisuke
E
Miuma
Satoshi
S
Eguchi
Katsumi
K
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006509:Hepatitis B / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology*; D022781:Hepatocytes / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D000410:Alanine Transaminase