Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection.
Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection.
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DOI：
10.1038/ni.1679
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发表时间：
2009-01
影响因子：
30.5
通讯作者：
Wherry, E. John
中科院分区：
文献类型：
--
作者：
Blackburn, Shawn D.;Shin, Haina;Haining, W. Nicholas;Zou, Tao;Workman, Creg J.;Polley, Antonio;Betts, Michael R.;Freeman, Gordon J.;Vignali, Dario A. A.;Wherry, E. John
T细胞耗竭通常发生在慢性感染期间，并阻止最佳病毒控制。然而，参与T细胞耗竭的分子途径仍然知之甚少。我们证明，由于多种抑制性受体的共表达，疲惫的CD 8 + T细胞会受到复杂的负调节层。耗尽的CD 8 + T细胞表达多达7种抑制性受体。多种不同抑制性受体的共表达与更大的T细胞耗竭和更严重的感染相关。通过多种抑制途径调节T细胞耗竭是非冗余的，因为体内同时阻断PD-1和LAG-3协同改善了T细胞应答并降低了病毒载量。因此，慢性病毒感染期间的CD 8 + T细胞应答受共表达的抑制性受体的复杂模式调节。
T cell exhaustion often occurs during chronic infections and prevents optimal viral control. The molecular pathways involved in T cell exhaustion, however, remain poorly understood. We demonstrate that exhausted CD8+ T cells are subject to complex layers of negative regulation due to co-expression of multiple inhibitory receptors. Exhausted CD8+ T cells expressed up to 7 inhibitory receptors. Co-expression of multiple distinct inhibitory receptors correlated with greater T cell exhaustion and more severe infection. Regulation of T cell exhaustion by diverse inhibitory pathways was non-redundant since blockade of PD-1 and LAG-3 simultaneously in vivo synergistically improved T cell responses and reduced viral load. Thus, CD8+ T cell responses during chronic viral infections are regulated by complex patterns of co-expressed inhibitory receptors.
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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：
64.5
作者：
Kaech, SM;Hemby, S;Ahmed, R
通讯作者：
Ahmed, R
DOI：
10.1084/jem.176.2.327
发表时间：
1992-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Baixeras E;Huard B;Miossec C;Jitsukawa S;Martin M;Hercend T;Auffray C;Triebel F;Piatier-Tonneau D
通讯作者：
Piatier-Tonneau D
影响因子：
56.9
作者：
Golub, TR;Slonim, DK;Lander, ES
通讯作者：
Lander, ES
影响因子：
5.4
作者：
Kotturi, Maya F.;Peters, Bjoern.;Sette, Alessandro
通讯作者：
Sette, Alessandro