Tim-3 expression defines a novel population of dysfunctional T cells with highly elevated frequencies in progressive HIV-1 infection.
Tim-3 expression defines a novel population of dysfunctional T cells with highly elevated frequencies in progressive HIV-1 infection.
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DOI：
10.1084/jem.20081398
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发表时间：
2008-11-24
期刊：
影响因子：
--
通讯作者：
Ostrowski MA
中科院分区：
文献类型：
--
作者：
Jones RB;Ndhlovu LC;Barbour JD;Sheth PM;Jha AR;Long BR;Wong JC;Satkunarajah M;Schweneker M;Chapman JM;Gyenes G;Vali B;Hyrcza MD;Yue FY;Kovacs C;Sassi A;Loutfy M;Halpenny R;Persad D;Spotts G;Hecht FM;Chun TW;McCune JM;Kaul R;Rini JM;Nixon DF;Ostrowski MA
T细胞功能的进行性丧失是人类免疫缺陷病毒1（HIV-1）慢性感染的标志。我们已经确定了一个新的人口功能失调的T细胞标记的糖蛋白蒂姆-3的表面表达。在HIV-1感染的个体中，这一群体的频率增加至HIV-1感染的慢性进展者中表达Tim-3的CD8 + T细胞的平均49.4 ± SD 12.9%，而在HIV-1未感染的个体中为28.5 ± 6.8%。HIV-1感染者T细胞上Tim-3表达水平与HIV-1病毒载量和CD 38表达呈正相关，与CD 4 + T细胞计数呈负相关。在进行性HIV-1感染中，HIV-1特异性CD8 + T细胞上的Tim-3表达上调。Tim-3表达的T细胞不能产生细胞因子或响应抗原增殖，并表现出受损的Stat5，Erk1/2和p38信号传导。阻断Tim-3信号通路恢复了HIV-1特异性T细胞的增殖并增强了细胞因子的产生。因此，Tim-3代表了治疗逆转HIV-1相关T细胞功能障碍的新靶点。
Progressive loss of T cell functionality is a hallmark of chronic infection with human immunodeficiency virus 1 (HIV-1). We have identified a novel population of dysfunctional T cells marked by surface expression of the glycoprotein Tim-3. The frequency of this population was increased in HIV-1–infected individuals to a mean of 49.4 ± SD 12.9% of CD8+ T cells expressing Tim-3 in HIV-1–infected chronic progressors versus 28.5 ± 6.8% in HIV-1–uninfected individuals. Levels of Tim-3 expression on T cells from HIV-1–infected inviduals correlated positively with HIV-1 viral load and CD38 expression and inversely with CD4+ T cell count. In progressive HIV-1 infection, Tim-3 expression was up-regulated on HIV-1–specific CD8+ T cells. Tim-3–expressing T cells failed to produce cytokine or proliferate in response to antigen and exhibited impaired Stat5, Erk1/2, and p38 signaling. Blocking the Tim-3 signaling pathway restored proliferation and enhanced cytokine production in HIV-1–specific T cells. Thus, Tim-3 represents a novel target for the therapeutic reversal of HIV-1–associated T cell dysfunction.
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通过PD-1-PD-1配体阻滞来振兴耗尽的HIV特异性T细胞。
影响因子：
15.3
作者：
Freeman, Gordon J.;Wherry, E. John;Ahmed, Rafi;Sharpe, Arlene H.
通讯作者：
Sharpe, Arlene H.
影响因子：
168.9
作者：
Hess, C;Altfeld, M;Luster, AD
通讯作者：
Luster, AD
DOI：
10.1084/jem.20060210
发表时间：
2006-06-12
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Koguchi K;Anderson DE;Yang L;O'Connor KC;Kuchroo VK;Hafler DA
通讯作者：
Hafler DA
影响因子：
6.4
作者：
Hunt, Peter W.;Brenchley, Jason;Deeks, Steven G.
通讯作者：
Deeks, Steven G.
影响因子：
3.8
作者：
Andersson, J;Behbahani, H;Fehniger, TE
通讯作者：
Fehniger, TE