Increased expression of CD40 ligand on systemic lupus erythematosus lymphocytes
Increased expression of CD40 ligand on systemic lupus erythematosus lymphocytes
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DOI：
10.1172/jci118855
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发表时间：
1996-08-01
影响因子：
15.9
通讯作者：
Crow, MK
中科院分区：
文献类型：
--
作者：
Koshy, M;Berger, D;Crow, MK
T细胞辅助B细胞活化和分化的特异性通过在T细胞受体介导的触发后在T细胞表面上短暂表达CD 40配体（CD 40 L）来维持。辅助性T细胞（T-h）CD 40 L与B细胞CD 40的相互作用诱导B细胞活化、细胞表面活化抗原表达、增殖和免疫球蛋白同种型转换的启动。我们预测，在系统性红斑狼疮（SLE）患者中，T-h细胞依赖性自身抗体的产生导致免疫复合物介导的组织损伤，CD 40 L表达可能增加、延长，正常人（n = 14）和风湿病对照组（n = 9）的T-h细胞经佛波酯（PMA）和离子霉素体外激活后，CD 40 L表达最高，在24和48小时观察到降低的水平。SLE患者（n = 19）的T-h细胞在培养的24和48 h内维持高水平的细胞表面CD 40 L表达。CD 40 L表达的延长在功能上是显著的，因为当与靶B细胞共培养时，24 h活化的SLE T细胞比24 h活化的正常T细胞诱导更高的B细胞表面CD 80（B7-1）表达。这些结果证明了SLE T细胞中CD 40 L表达的调节受损，并确定了这种系统性自身免疫性疾病治疗的重要潜在靶点。
The specificity of T cell help for B cell activation and differentiation is maintained by the brief expression on the T cell surface, following T cell receptor-mediated triggering, of CD40 ligand (CD40L). Interaction of T helper (T-h) cell CD40L with B cell CD40 induces B cell activation, cell surface expression of activation antigens, proliferation, and initiation of immunoglobulin isotype switch, We predicted that in patients with systemic lupus erythematosus (SLE), in whom T-h cell-dependent production of autoantibodies results in immune complex-mediated tissue damage, CD40L expression might be augmented, prolonged, or abnormally regulated, Baseline expression of CD40L was increased in some SLE patients studied, when compared with control subjects, While T-h cells from normal subjects (n = 14) and rheumatic disease control patients (n = 9) showed maximal expression of CD40L, after in vitro activation with phorbol myristate acetate (PMA) and ionomycin, at 6 h of culture with diminished levels observed at 24 and 48 h. T-h cells from SLE patients (n = 19) maintained high level cell surface expression of CD40L through 24 and 48 h of culture, The prolonged expression of CD40L was functionally significant, as 24 h-activated SLE T cells, when cocultured with target B cells, induced greater B cell surface CD80 (B7-1) expression than did 24 h-activated normal T cells. These results document impaired regulation of CD40L expression in SLE T cells and identify an important potential target for therapy in this systemic autoimmune disease.