Migration of Th1 lymphocytes is regulated by CD152 (CTLA-4)-mediated signaling via PI3 kinase-dependent Akt activation.
Migration of Th1 lymphocytes is regulated by CD152 (CTLA-4)-mediated signaling via PI3 kinase-dependent Akt activation.
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DOI：
10.1371/journal.pone.0031391
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Brunner-Weinzierl MC
中科院分区：
文献类型：
--
作者：
Knieke K;Lingel H;Chamaon K;Brunner-Weinzierl MC
有效的获得性免疫反应需要在次级淋巴器官和炎症组织中定位T淋巴细胞。为了实现T淋巴细胞的正确定位，这些细胞的迁移是由黏附分子和趋化因子启动和指导的。最近的研究表明，抑制表面分子CD152(CTLA-4)可启动Th细胞的迁移，但其分子机制尚不清楚。利用OVA特异性TCR转基因CD152缺陷小鼠和CD152功能正常小鼠的CD4T淋巴细胞，我们证明了CD152通过依赖于磷脂酰肌醇3-激酶(PI3K)激活蛋白激酶B(PKB/Akt)对趋化因子触发的信号转导进行了差异调节。在CD152信号存在的情况下，趋化剂CCL4通过苏氨酸308和丝氨酸473的磷酸化选择性地诱导表达同源趋化因子受体CCR5的致炎Th淋巴细胞中Akt的完全激活。AKT信号导致细胞骨架重排，这对迁移是必不可少的。因此，CD152信号影响T细胞迁移的这种新的Akt调节功能表明，增强CD152或其下游信号转导可以帮助旨在敏化T淋巴细胞实现最佳迁移的治疗，从而有助于准确和有效的免疫反应。
Efficient adaptive immune responses require the localization of T lymphocytes in secondary lymphoid organs and inflamed tissues. To achieve correct localization of T lymphocytes, the migration of these cells is initiated and directed by adhesion molecules and chemokines. It has recently been shown that the inhibitory surface molecule CD152 (CTLA-4) initiates Th cell migration, but the molecular mechanism underlying this effect remains to be elucidated. Using CD4 T lymphocytes derived from OVA-specific TCR transgenic CD152-deficient and CD152-competent mice, we demonstrate that chemokine-triggered signal transduction is differentially regulated by CD152 via phosphoinositide 3-kinase (PI3K)-dependent activation of protein kinase B (PKB/Akt). In the presence of CD152 signaling, the chemoattractant CCL4 selectively induces the full activation of Akt via phosphorylation at threonine 308 and serine 473 in pro-inflammatory Th lymphocytes expressing the cognate chemokine receptor CCR5. Akt signals lead to cytoskeleton rearrangements, which are indispensable for migration. Therefore, this novel Akt-modulating function of CD152 signals affecting T cell migration demonstrates that boosting CD152 or its down-stream signal transduction could aid therapies aimed at sensitizing T lymphocytes for optimal migration, thus contributing to a precise and effective immune response.
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DOI：
10.1084/jem.20031058
发表时间：
2004-03-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Pandiyan P;Gärtner D;Soezeri O;Radbruch A;Schulze-Osthoff K;Brunner-Weinzierl MC
通讯作者：
Brunner-Weinzierl MC
影响因子：
4.4
作者：
Rudolph, Marion;Hebel, Katrin;Brunner-Weinzierl, Monika C.
通讯作者：
Brunner-Weinzierl, Monika C.
影响因子：
4.4
作者：
Debes, GF;Höpken, UE;Hamann, A
通讯作者：
Hamann, A
DOI：
10.4049/jimmunol.0903851
发表时间：
2010-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Morley SC;Wang C;Lo WL;Lio CW;Zinselmeyer BH;Miller MJ;Brown EJ;Allen PM
通讯作者：
Allen PM
影响因子：
3.2
作者：
Penela, Petronila;Ribas, Catalina;Mayor, Federico, Jr.
通讯作者：
Mayor, Federico, Jr.