Effects of interferon-β on co-signaling molecules: upregulation of CD40, CD86 and PD-L2 on monocytes in relation to clinical response to interferon-β treatment in patients with multiple sclerosis
Effects of interferon-β on co-signaling molecules: upregulation of CD40, CD86 and PD-L2 on monocytes in relation to clinical response to interferon-β treatment in patients with multiple sclerosis
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干扰素-β 对协同信号分子的影响：单核细胞上 CD40、CD86 和 PD-L2 的上调与多发性硬化症患者对干扰素-β 治疗的临床反应相关
DOI：
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
A. Windhagen
中科院分区：
文献类型：
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作者：
E. Wiesemann;M. Deb;C. Trebst;B. Hemmer;M. Stangel;A. Windhagen
干扰素-β（IFN-β）降低复发缓解型多发性硬化（MS）患者亚组的疾病活动性。对IFN-β的反应性的作用机制以及病理生理学基础尚不清楚。由于T细胞活化在MS的病理生理学中起着重要作用，因此我们在此研究了IFN-β对MS患者中共信号通路（CD 28-CD 80/CD 86、CD 154-CD 40、ICOS-ICOSL、PD-1-PD-L1/2）表达的影响，并将结果与个体患者对IFN-β的临床反应相关联。通过流式细胞术在与IFN-β孵育后的外周血单个核细胞上体外测量共信号分子的表达，以及在32名未治疗的MS患者和24名IFN-β治疗的MS患者（包括13名纵向患者）的全血样品中体内测量共信号分子的表达。IFN-β处理在体外和体内诱导单核细胞上的CD 40、CD 80、CD 86、PD-L1和PD-L2以及CD 4 +-T细胞上的PD-L1的上调。根据Kurtzkés EDSS（扩展残疾状态量表）进展和复发率，将IFN-β治疗的MS患者分为应答者和非应答者。单核细胞上的CD 40、CD 86和PD-L2的上调与对IFN-β的治疗反应相关（分别为P < 0.001、P = 0.028和P = 0.028）。我们的研究结果表明，IFN-β在体外和体内上调共刺激和共抑制分子，暗示调节正性和负性共刺激信号之间的平衡可能是IFN-β在MS中作用机制的重要部分。CD 86和PD-L2可作为IFN-β治疗早期临床应答的预测标志物。多发性硬化2008; 14：166-176. http://msj.sagepub.com
Interferon-beta (IFN-β) reduces disease activity in a subgroup of patients with relapsing remitting multiple sclerosis (MS). The mechanism of action as well as the pathophysiological basis of responsiveness to IFN-β is not well understood. Since T-cell activation plays an important part in the pathophysiology of MS, we here investigated the effect of IFN-β on the expression of co-signaling pathways (CD28—CD80/CD86, CD154—CD40, ICOS—ICOSL, PD-1—PD-L1/2) in MS patients and correlated the results with the clinical response to IFN-β in individual patients. Expression of co-signaling molecules was measured by flow cytometry in vitro on peripheral blood mononuclear cells after incubation with IFN-β, and in vivo in whole blood samples of 32 untreated and 24 IFN-β treated MS patients, including 13 patients longitudinal. IFN-β treatment induced upregulation of CD40, CD80, CD86, PD-L1 and PD-L2 on monocytes as well as PD-L1 on CD4+-T-cells in vitro and in vivo. IFN-β treated MS patients were grouped into responders and non-responders on the basis of Kurtzkés EDSS (expanded disability status scale) progression and relapse rate. Upregulation of CD40, CD86 and PD-L2 on monocytes was associated with treatment response to IFN-β (P < 0.001, P = 0.028 and P = 0.028, respectively). Our results show that IFN-β upregulates co-stimulatory as well as co-inhibitory molecules in vitro and in vivo implicating that modulation of the balance between positive and negative co-stimulatory signals might be an important part of the mechanism of action of IFN-β in MS. Upregulation of the expression of CD40, CD86 and PD-L2 may be useful as a predictive marker for clinical response to IFN-β treatment at early timepoints during IFN-β therapy. Multiple Sclerosis 2008; 14: 166—176. http://msj.sagepub.com
影响因子：
8.6
作者：
R. Sporici;Richard L. Beswick;C. Allmen;C. A. Rumbley;M. Hayden-Ledbetter;J. Ledbetter;P. Perrin
通讯作者：
R. Sporici;Richard L. Beswick;C. Allmen;C. A. Rumbley;M. Hayden-Ledbetter;J. Ledbetter;P. Perrin
DOI：
10.1073/pnas.93.6.2499
发表时间：
1996-03-19
影响因子：
11.1
作者：
Gerritse, K;Laman, JD;Claassen, E
通讯作者：
Claassen, E