Hyperexpression of CD40 ligand by B and T cells in human lupus and its role in pathogenic autoantibody production
Hyperexpression of CD40 ligand by B and T cells in human lupus and its role in pathogenic autoantibody production
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DOI：
10.1172/jci118643
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发表时间：
1996-05-01
影响因子：
15.9
通讯作者：
Datta, SK
中科院分区：
文献类型：
--
作者：
DesaiMehta, A;Lu, LJ;Datta, SK
我们研究了共刺激分子CD40及其配体CD40L在SLE发病机制中的作用。与正常受试者或缓解期患者相比，活动性狼疮患者PBMC中表达CD 40 L的CD 4（+）T细胞的频率增加了21倍。然而，自体B细胞上的CD 40分子同样可以下调狼疮或正常T细胞中由促有丝分裂刺激诱导的CD 40 L表达。活动性狼疮患者表达CD40L的CD8（+）T细胞百分比也增加了22倍，这与SLE患者异常的辅助活性一致。令人惊讶的是，活动性狼疮患者的自发表达高水平CD40 L的B细胞增加了20.5倍，与他们的T细胞一样强烈。尽管缓解期狼疮患者的CD40 L（+）细胞水平在正常受试者的范围内，但在他们的T和B细胞中，丝裂原诱导的CD40 L表达的上调明显大于正常，表明存在内在缺陷，抗CD 40 L的单克隆抗体在体外能显著阻断狼疮患者淋巴细胞产生抗核自身抗体的能力，为抗CD 40 L免疫治疗狼疮提供了可能。未来对CD 40 L高表达的研究可能阐明狼疮致病性T和B细胞的调节缺陷。
We investigated the role of the costimulatory molecules, CD40 and its ligand CD40L, in the pathogenesis of human SLE. In comparison to normal subjects or patients in remission, PBMC from active lupus patients had a 21-fold increase in the frequency of CD40L-expressing, CD4(+) T cells, However, the expression of CD40L induced in either lupus or normal T cells by mitogenic stimulation could be downregulated equally well by CD40 molecules on autologous B cells. Active lupus patients also had a 22-fold increase in percentage of CD8(+) T cells expressing CD40L, consistent with their unusual helper activity in SLE. Surprisingly, patients with active lupus had a 20.5-fold increase in B cells that spontaneously expressed high levels of CD40L, as strongly as their T cells, Although lupus patients in remission had low levels of CD40L(+) cells in the range of normal subjects, mitogen-induced upregulation of CD40L expression in their T and B cells was markedly greater than normal, suggesting an intrinsic defect, A mAb to CD40L blocked significantly the ability of lymphocytes from lupus patients with active and established disease to produce the pathogenic variety of antinuclear autoantibodies in vitro, bolstering the possibility of anti-CD40L immunotherapy for lupus, Future studies on the hyperexpression of CD40L could elucidate a regulatory defect in the pathogenic T and B cells of lupus.