These authors contributed equally to this work.
Hypercytolytic activity of hepatic natural killer cells correlates with liver injury in chronic hepatitis B patients†
Version of Record online: 26 OCT 2010
Copyright © 2010 American Association for the Study of Liver Diseases
Volume 53, Issue 1, pages 73–85, January 2011
How to Cite
Zhang, Z., Zhang, S., Zou, Z., Shi, J., Zhao, J., Fan, R., Qin, E., Li, B., Li, Z., Xu, X., Fu, J., Zhang, J., Gao, B., Tian, Z. and Wang, F.-S. (2011), Hypercytolytic activity of hepatic natural killer cells correlates with liver injury in chronic hepatitis B patients. Hepatology, 53: 73–85. doi: 10.1002/hep.23977
Potential conflict of interest: Nothing to report.
- Issue online: 12 JAN 2011
- Version of Record online: 26 OCT 2010
- Accepted manuscript online: 10 SEP 2010 09:53AM EST
- Manuscript Accepted: 29 AUG 2010
- Manuscript Received: 30 MAR 2010
- National Grand Program on Key Infectious Diseases. Grant Numbers: 2009ZX10004-309, 2008ZX10002-007, 2008ZX10002-005-6
- National Key Basic Research Program of China. Grant Numbers: 2007CB512805, 2007CB512804, 2009CB522507
- Key Program of the National Natural Science Foundation of China. Grant Number: 30730088
- National Natural Science Foundation of China. Grant Number: 30972752
Additional Supporting Information may be found in the online version of this article.
|HEP_23977_sm_SuppInfoFigure1.tif||7836K||Supporting Figure 1. The quantitative analysis of CD56+ (A) and CD3+ (B) cells in both portal and lobular areas in the liver tissues of these subjects. Each dot represents one individual. The horizontal bars indicate the median percentiles. The significant P values are shown. hpf, high-power field.|
|HEP_23977_sm_SuppInfoFigure2.tif||5634K||Supporting Figure 2. The gating strategy of intrahepatic NK cells. Gate 1 was used to select CD45+ cells and to exclude red blood cells and cell debris. Gate 2 was used to separate liver-infiltrating lymphocytes from other cells (excluding monocytes and granulocytes) by forward and side scatter. Finally, the cell subsets including CD3-CD56+ NK cells (left-upper quadrants), CD3+CD56+ NKT cells (right-upper quadrants) and CD3+CD56− T cells (right-lower quadrants) were selected.|
|HEP_23977_sm_SuppInfoFigure3.tif||17529K||Supporting Figure 3. Representative dot plots depict the expression of activation receptors (NKp30, NKp44, NKp46 and NKG2D) and inhibitory receptors (CD158a, CD158b and NKG2A) in NK cells from LILs and PBMCs in the three groups. CD3−CD56+ NK cells were gated. Values in the upper-right quadrants represent the percentages of CD3−CD56+ NK cells that express NK receptors. LILs, liver-infiltrating lymphocytes; PBMCs, peripheral blood mononuclear cells; HC, healthy controls; IT, immune tolerant subjects with chronic HBV infection; IA, immune activated patients with chronic HBV infection.|
|HEP_23977_sm_SuppInfoFigure4.tif||12407K||Supporting Figure 4. The spontaneous degranulation of NK cells was significantly increased in IA patients. (A) Representative dot plots depict the spontaneous degranulation of both intrahepatic and peripheral NK cells among IA patients and IT and HC subjects. CD3−CD56+ NK cells were gated. Values in the upper-right quadrants represent the percentages of CD3−CD56+ NK cells that express CD107a. (B) Pooled data show the percentages of intrahepatic and peripheral CD3−CD56+ NK cells that express CD107a from the three groups. Each dot represents one individual. The horizontal bars indicate the median percentiles. Multiple comparisons were made using the Kruskal-Wallis H non-parametric test among the different groups. The Mann-Whitney U test was used to compare data from two different groups. The significant P values are shown.|
|HEP_23977_sm_SuppInfoFigure5.tif||6679K||Supporting Figure 5. NKp30 predominantly accounted for the NCR-mediated NK cell degranulation seen in IA patients. The redirected assay of NK cells against P815 target cells using mixed anti-NCR Abs or individual anti-NKp30, NKp44 and NKp46 antibodies was performed. Pooled data show the percentages of NK cells expressing IFN-? (A) and CD107a (B) in the redirected assay. The Wilcoxon matched pairs T test was used to compare the data from same individuals. *P < 0.05.|
|HEP_23977_sm_SuppInfoFigure6.tif||10694K||Supporting Figure 6. Hepatic mRNA expression analysis of NK receptor ligands in IA patients and HC and IT subjects. Statistical analysis of the mRNA expression of the ligands of NK receptors in the liver, including the NKG2D ligands, MICa, MICb, ULBP1, 2, 3 and 4, the NKG2A ligand, HLA-E, and NKp30 ligands, BAT3 and B7H6, from IA patients (n = 10) and IT (n = 6) and HC subjects (n = 7). The Mann-Whitney U test was used to compare data from two different groups. The P values are shown.|
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