Cardiolipin binds to CD1d and stimulates CD1d-restricted γδ T cells in the normal murine repertoire.
Cardiolipin binds to CD1d and stimulates CD1d-restricted γδ T cells in the normal murine repertoire.
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DOI：
10.4049/jimmunol.1000921
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发表时间：
2011-04-15
期刊：
影响因子：
--
通讯作者：
Rauch J
中科院分区：
文献类型：
--
作者：
Dieudé M;Striegl H;Tyznik AJ;Wang J;Behar SM;Piccirillo CA;Levine JS;Zajonc DM;Rauch J
心磷脂（CL）是细菌细胞壁中的主要磷脂，在哺乳动物线粒体中与免疫系统隔离，因此是潜在的“危险信号”。基于越来越多的证据表明，磷脂构成的天然配体的CD 1和CD 1d限制性T细胞识别磷脂，我们假设，CD 1d结合并提出CL，在正常的免疫库中的T细胞响应CL在CD 1d限制性的方式。我们在2.3 μ m分辨率下测定了鼠CD 1d-CL晶体结构，并通过额外的脂质负载实验确定了CL（一种四酰化磷脂）与鼠CD 1d结合，其中两条烷基链埋在CD 1d结合沟内，其余两条暴露在溶剂中。我们还证明了CL的功能刺激活性，表明健康小鼠的脾和肝γδ T细胞在体外以剂量依赖性和CD 1d限制性方式对哺乳动物或细菌CL产生反应，迅速分泌细胞因子干扰素-γ和RANTES。最后，我们发现，肝γδ T细胞在体内激活的CD 1d-轴承树突状细胞已与CL脉冲，但不是，磷脂酰胆碱。总之，这些研究结果表明，CD 1d能够结合CL并将CL呈递给健康小鼠脾脏和肝脏中存在的CL响应性γδ T细胞亚群，并表明这些细胞可能在宿主对细菌脂质的反应中发挥作用，并可能在自身CL中发挥作用。我们认为CL应答性γδ T细胞在感染和组织损伤期间的免疫监视中发挥作用。
Cardiolipin (CL), a major phospholipid in bacterial cell walls, is sequestered from the immune system in mammalian mitochondria and is, therefore, a potential “danger signal”. Based on growing evidence that phospholipids constitute natural ligands for CD1 and that CD1d-restricted T cells recognize phospholipids, we hypothesized that CD1d binds and presents CL, and that T cells in the normal immune repertoire respond to CL in a CD1d-restricted manner. We determined the murine CD1d-CL crystal structure at 2.3 Å resolution and established through additional lipid loading experiments that CL, a tetra-acylated phospholipid, binds to murine CD1d with two alkyl chains buried inside the CD1d binding groove and the remaining two exposed into the solvent. We furthermore demonstrate the functional stimulatory activity of CL, showing that splenic and hepatic γδ T cells from healthy mice proliferate in vitro in response to mammalian or bacterial CL in a dose-dependent and CD1d-restricted manner, rapidly secreting the cytokines interferon-γ and RANTES. Finally, we show that hepatic γδ T cells are activated in vivo by CD1d-bearing dendritic cells that have been pulsed with CL, but not, phosphatidylcholine. Together, these findings demonstrate that CD1d is able to bind and present CL to a subset of CL-responsive γδ T cells that exist in the spleen and liver of healthy mice, and suggest that these cells could play a role in host responses to bacterial lipids and, potentially, self-CL. We propose that CL-responsive γδ T cells play a role in immune surveillance during infection and tissue injury.
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影响因子：
6.4
作者：
Jason, J;Buchanan, I;Jarvis, WR
通讯作者：
Jarvis, WR
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
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作者：
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通讯作者：
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作者：
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影响因子：
16.8
作者：
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通讯作者：
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