Tim-3 expression on peripheral T cell subsets correlates with disease progression in hepatitis B infection.
Tim-3 expression on peripheral T cell subsets correlates with disease progression in hepatitis B infection.
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外周 T 细胞亚群的 Tim-3 表达与乙型肝炎感染的疾病进展相关
DOI：
10.1186/1743-422x-8-113
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发表时间：
2011-03-11
期刊：
影响因子：
4.8
通讯作者：
Zheng M
中科院分区：
文献类型：
--
作者：
Wu W;Shi Y;Li J;Chen F;Chen Z;Zheng M
背景与目的T细胞免疫球蛋白结构域和粘蛋白结构域含分子3（Tim-3）是慢性病毒性疾病中T细胞功能障碍的新机制。然而，Tim-3在慢性B型肝炎（CH B）发病机制中的作用还不清楚。方法收集40例慢性乙型肝炎患者外周血标本，其中中度慢性乙型肝炎（MCHB）23例，重度慢性乙型肝炎（SCHB）17例。对照样本来自9名急性B型肝炎（AHB）患者和26名年龄匹配的健康受试者。Tim-3在T细胞上的表达通过流式细胞术测定。结果Tim-3在AHB和CHB患者外周血CD 4+和CD 8 +T细胞上的表达与健康对照组相比升高。Tim-3+T细胞的百分比在SCHB患者中相对于MCHB患者进一步增加，并且与肝损伤的常规标志物（丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、总胆红素（TB）和国际标准化比率（INR）水平）呈正相关。Tim-3表达T细胞的频率与T-bet mRNA表达和血浆干扰素-γ（INF-γ）水平呈负相关。此外，Tim-3表达CD 4+或CD 8 +T细胞减少慢性乙型肝炎患者的疾病缓解后，抗病毒治疗和AHB患者在恢复phase.ConclusionsOur结果表明，过度表达的Tim-3参与慢性乙型肝炎的疾病进展和Tim-3可能参与偏斜的Th 1/Tc 1反应，这有助于HBV感染的持久性。
Background and objectiveT-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3) represents a novel mechanism of T-cell dysfunction in chronic viral diseases. However, the role of Tim-3 in the pathogenesis of chronic hepatitis B (CHB) is not well understood. We investigated Tim-3 expression on peripheral T cell subsets and analyzed the relationship between Tim-3 expression and disease progression in HBV infection.Methodsperipheral blood samples were obtained from CHB patients (n = 40), including 23 patients with moderate CHB [MCHB] and 17 with severe CHB [SCHB]. Control samples were obtained from nine acute hepatitis B patients (AHB) and 26 age-matched healthy subjects. The expression of Tim-3 on T cells was determined by flow cytometry.ResultsTim-3 expression was elevated on peripheral CD4+and CD8+T cells from AHB and CHB patients compared to those from healthy controls. The percentage of Tim-3+T cells was further increased in SCHB patients relative to MCHB patients and showed a positive correlation with conventional markers for liver injury (alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TB) and international normalized ratio (INR) level). The frequency of Tim-3-expressing T cells was negatively correlated with T-bet mRNA expression and plasma interferon-gamma (INF-gamma) levels. Further, Tim-3 expression on CD4+or CD8+T cells was reduced in CHB patients with disease remission after antiviral treatment and in AHB patients during the convalescence phase.ConclusionsOur results suggest that over-expression of Tim-3 is involved in disease progression of CHB and that Tim-3 may participate in skewing of Th1/Tc1 response, which contributes to persistency of HBV infection.