Rong Y-H, Wan Z-H, Song H, Li Y-L, Zhu B, Zang H, Zhao Y, Liu H-L, Zhang A-M, Xiao L, Xin S-J, You S-L
Medical School of Chinese PLA, Beijing, China; Liver Failure Treatment and Research Center, Beijing 302 Hospital, Beijing, China.
Tissue Antigens. 2014 Feb;83(2):76-81. doi: 10.1111/tan.12278. Epub 2014 Jan 7.
Hepatitis B virus (HBV) infection is one of the major causes of chronic liver inflammation. Tim-3 acts as a negative regulatory molecule and plays a critical role in immune tolerance. In the current study, we investigated Tim-3 expression on peripheral monocytes and CD3+CD16/CD56+ natural killer like T (NKT-like) cells in chronic hepatitis B (CHB) patients. Peripheral blood mononuclear cells (PBMCs) were isolated from 52 CHB patients and 60 healthy controls. Tim-3+CD14+ cells and Tim-3+CD3+CD16/CD56+ cells were analyzed by flow cytometry. Results showed that expression of Tim-3 was significantly increased on both the monocytes and NKT-like cells in CHB patients than in controls (P = 0.002 and P < 0.001, respectively). Tim-3 levels on monocytes and NKT-like cells were further upregulated in patients with acute-on-chronic liver failure (ACLF). In addition, we assessed the correlation of Tim-3 expression with levels of alanine aminotransferase (ALT) and tumor necrosis factor alpha (TNF-α). Data revealed that Tim-3 expression on both monocytes and NKT-like cells was positively correlated with level of ALT (r = 0.59, P < 0.001, and r = 0.60, P < 0.001, respectively), whereas Tim-3 expression on NKT-like cells was negatively correlated with serum level of TNF-α (r = -0.54, P < 0.001) in CHB patients. Our results suggest that Tim-3 may play important roles in the pathogenesis of CHB.
乙型肝炎病毒（HBV）感染是慢性肝脏炎症的主要原因之一。Tim-3作为一种负调控分子，在免疫耐受中起关键作用。在本研究中，我们调查了慢性乙型肝炎（CHB）患者外周血单核细胞和CD3+CD16/CD56+自然杀伤样T（NKT样）细胞上Tim-3的表达情况。从52例CHB患者和60例健康对照者中分离外周血单个核细胞（PBMC）。通过流式细胞术分析Tim-3+CD14+细胞和Tim-3+CD3+CD16/CD56+细胞。结果显示，CHB患者单核细胞和NKT样细胞上Tim-3的表达均显著高于对照组（P分别为0.002和P<0.001）。慢性加急性肝衰竭（ACLF）患者单核细胞和NKT样细胞上的Tim-3水平进一步上调。此外，我们评估了Tim-3表达与丙氨酸转氨酶（ALT）和肿瘤坏死因子α（TNF-α）水平的相关性。数据显示，CHB患者单核细胞和NKT样细胞上Tim-3的表达均与ALT水平呈正相关（r分别为0.59，P<0.001和r为0.60，P<0.001），而CHB患者NKT样细胞上Tim-3的表达与血清TNF-α水平呈负相关（r=-0.54，P<0.001）。我们的结果表明，Tim-3可能在CHB的发病机制中起重要作用。
