CD40-CD40 ligand interactions in experimental allergic encephalomyelitis and multiple sclerosis
CD40-CD40 ligand interactions in experimental allergic encephalomyelitis and multiple sclerosis
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DOI：
10.1073/pnas.93.6.2499
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发表时间：
1996-03-19
影响因子：
11.1
通讯作者：
Claassen, E
中科院分区：
文献类型：
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作者：
Gerritse, K;Laman, JD;Claassen, E
我们研究了CD40-CD40配体（CD40L）相互作用在多发性硬化症（MS）和实验性过敏性脑脊髓炎（EAE）中的作用。表达CD40L （gp39）表面蛋白的活化辅助性T细胞在MS患者的脑组织切片中被发现，但在正常对照或其他神经系统疾病患者的脑组织切片中未被发现。在活动性病变（血管周围浸润）中，cd40l阳性细胞与cd40携带细胞共定位。这些携带CD40的细胞大多数是单核细胞（巨噬细胞或小胶质细胞），相对较少的是B细胞。为了从功能上评价CD40-CD40L相互作用，我们通过蛋白脂肽免疫在小鼠中诱导EAE。抗cd40l单克隆抗体治疗完全阻止了疾病的发展。此外，即使在疾病发病后，在达到最大残疾评分前不久，给予抗cd40l单克隆抗体也能显著减少疾病。MS患者和EAE动物脑组织中存在表达CD40L的辅助性T细胞，以及动物模型成功的实验预防和治疗提供的功能证据表明，阻断cd40 -CD40L介导的细胞相互作用可能是干扰活性MS的一种方法。
We investigated the role of CD40-CD40 ligand (CD40L) interactions in multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE). Activated helper T cells expressing CD40L (gp39) surface protein were found in MS patient brain sections, but not in brain tissue sections of normal controls or patients with other neurological diseases. CD40L-positive cells were co-localized with CD40-bearing cells in active lesions (perivascular infiltrates). Most of these CD40 bearing cells proved to be of the monocytic lineage (macrophages or microglial cells), and relatively few were B cells. To functionally evaluate CD40-CD40L interactions, EAE was elicited in mice by means of proteolipid-peptide immunization. Treatment with anti-CD40L monoclonal antibody completely prevented the development of disease. Furthermore, administration of anti-CD40L monoclonal antibody, even after disease onset, shortly before maximum disability score was reached led to dramatic disease reduction. The presence of helper T cells expressing CD40L in brain tissue of MS patients and EAE animals, together with the functional evidence provided by successful experimental prevention and therapy in an animal model, indicates that blockade of CD40-CD40L-mediated cellular interactions may be a method for interference in active MS.