The role of SAP in murine CD150 (SLAM)-mediated T-cell proliferation and interferon γ production
The role of SAP in murine CD150 (SLAM)-mediated T-cell proliferation and interferon γ production
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DOI：
10.1182/blood-2002-02-0445
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发表时间：
2002-10-15
期刊：
影响因子：
20.3
通讯作者：
Terhorst, C
中科院分区：
文献类型：
--
作者：
Howie, D;Okamoto, S;Terhorst, C
CD150（信号淋巴细胞激活分子[SLAM]）是一种在T细胞、B细胞、巨噬细胞和树突状细胞上表达的自身配体细胞表面糖蛋白。为了进一步探究CD150信号在共刺激和Th1细胞启动中的作用，我们制备了一组大鼠抗小鼠CD150单克隆抗体。在活化的T细胞以及脂多糖/干扰素γ（IFN -γ）活化的巨噬细胞中，CD150细胞表面表达以快速的动力学方式上调。抗CD150触发可对通过CD3触发的T细胞产生强烈的共刺激作用。抗CD150诱导的小鼠T细胞的DNA合成不依赖于SLAM相关蛋白（SAP，SH2D1A），因为抗CD150在SAP（-/-）T细胞中诱导的DNA合成水平相似。在初次刺激过程中，抗CD150抗体还可增强野生型和SAP（-/-）T细胞中IFN -γ的产生。SAP（-/-）T细胞中IFN -γ的产生水平高于野生型T细胞。在Th1细胞启动过程中，抗CD150抗体还与白细胞介素12（IL - 12）处理协同上调IL - 12受体β2 mRNA，并以IFN -γ依赖的方式抑制初始Th2极化。在CD4 T细胞上交联CD150可诱导Akt/PKB的快速丝氨酸磷酸化。我们推测这是一条对CD150介导的T细胞增殖有重要作用的途径。
CD150 (signaling lymphocyte activation molecule [SLAM]) is a self-ligand cell surface glycoprotein expressed on T cells, B cells, macrophages, and dendritic cells. To further explore the role of CD150 signaling in costimulation and T(H)1 priming we have generated a panel of rat anti-mouse CD150 monoclonal antibodies. CD150 cell surface expression is upregulated with rapid kinetics in activated T cells and lipopolysaccharide/interferon gamma (IFN-gamma)-activated macrophages. Anti-CD150 triggering induces strong costimulation of T cells triggered through CD3. DNA synthesis of murine T cells induced by anti-CD150 is not dependent on SLAM-associated protein (SAP, SH2D1A), because anti-CD150 induces similar levels of DNA synthesis in SAP(-/-) T cells. Antibodies to CD150 also enhance IFN-gamma production both in wild-type and SAP(-/-) T cells during primary stimulation. The level of IFN-gamma production is higher in SAP(-/-) T cells than in wild-type T cells. Anti-CD150 antibodies also synergize with interleukin 12 (IL-12) treatment in up-regulation of IL-12 receptor beta(2) mRNA during T(H)1 priming, and inhibit primary T(H)2 polarization in an IFN-gamma-dependent fashion. Crosslinking CD150 on CD4 T cells induces rapid serine phosphorylation of Akt/PKB. We speculate that this is an important pathway contributing to CD150-mediated T-cell proliferation.