LAG-3 Confers a Competitive Disadvantage upon Antiviral CD8+ T Cell Responses.
LAG-3 Confers a Competitive Disadvantage upon Antiviral CD8+ T Cell Responses.
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DOI：
10.4049/jimmunol.1401594
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发表时间：
2016-07-01
期刊：
影响因子：
--
通讯作者：
Whitmire JK
中科院分区：
文献类型：
--
作者：
Cook KD;Whitmire JK
正在进行的临床试验正在评估全身阻断淋巴细胞活化基因-3（LAG-3）信号以提高对肿瘤的免疫力的益处。这些研究是基于LAG-3在慢性病毒感染和抗肿瘤应答期间调节CD 8 + T细胞的公认抑制作用。然而，LAG-3缺陷小鼠的T细胞应答在大小和功能上与野生型动物相似，表明LAG-3具有细微的免疫调节功能。我们在小鼠中进行了一系列过继转移实验，以更好地理解LAG-3在调节CD 8 + T细胞应答中的T细胞内在功能。我们的研究结果表明，LAG-3表达的CD 8 + T细胞抑制其竞争的适应性，并导致在一个轻微降低的细胞分裂率相比，LAG-3缺陷细胞。LAG-3的这种细胞内在效应在急性和慢性病毒感染中是一致的。这些数据表明，LAG-3直接调节T细胞应答的大小，并支持使用LAG-3阻断方案来增强CD 8 + T细胞应答。
Ongoing clinical trials are evaluating the benefits of systemic blockade of lymphocyte activation gene-3 (LAG-3) signals to improve immunity to tumors. Those studies are founded on the well-established inhibitory role of LAG-3 in regulating CD8+ T cells during chronic virus infection and anti-tumor responses. However, the T cell response in LAG-3 deficient mice is similar in size and function to that in wild type animals, suggesting LAG-3 has nuanced immune-regulatory functions. We performed a series of adoptive transfer experiments in mice to better understand the T cell-intrinsic functions of LAG-3 in the regulation of CD8+ T cell responses. Our results indicate that LAG-3 expression by CD8+ T cells inhibits their competitive fitness and results in a slightly reduced rate of cell division in comparison to LAG-3 deficient cells. This cell-intrinsic effect of LAG-3 was consistent across both acute and chronic virus infections. These data show that LAG-3 directly modulates the size of the T cell response and support the use of LAG-3 blockade regimens to enhance CD8+ T cell responses.
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影响因子：
30.5
作者：
Butler, Noah S.;Moebius, Jacqueline;Pewe, Lecia L.;Traore, Boubacar;Doumbo, Ogobara K.;Tygrett, Lorraine T.;Waldschmidt, Thomas J.;Crompton, Peter D.;Harty, John T.
通讯作者：
Harty, John T.
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：
5.4
作者：
Grayson, Jason M.;Weant, Ashley E.;Hildeman, David
通讯作者：
Hildeman, David
影响因子：
4.4
作者：
Andreae, S;Piras, F;Triebel, F
通讯作者：
Triebel, F
影响因子：
30.5
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
通讯作者：
Wherry, E. John