Interaction between CD40 and its ligand gp39 in the development of murine lupus nephritis.
Interaction between CD40 and its ligand gp39 in the development of murine lupus nephritis.
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DOI：
10.4049/jimmunol.154.3.1470
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发表时间：
1995-02
影响因子：
4.4
通讯作者：
C. Mohan;Y. Shi;J. Laman;S. Datta
中科院分区：
文献类型：
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作者：
C. Mohan;Y. Shi;J. Laman;S. Datta
我们研究了gp 39-CD 40相互作用在狼疮小鼠肾小球肾炎发展中的作用。与正常小鼠相比，狼疮小鼠的脾脏中gp 39 + T细胞的比例更高，即使在自身免疫前1个月的年龄，gp 39表达的进一步增加抗CD 3抗体刺激显着更大的狼疮T细胞。抗gp 39抗体在体外可阻断狼疮鼠Th克隆和脾Th细胞的致病性自身抗体诱导能力。加速狼疮性肾炎的病原性自身抗体诱导Th克隆在体内的转移也可以完全阻断抗gp 39抗体。令人惊讶的是，用抗gp 39抗体对狼疮小鼠进行短暂治疗，在抗体从其系统中清除后很长一段时间内，对它们的自发性疾病具有持续的有益作用。只有三次注射抗gp 39抗体给予3个月龄的prenephritic狼疮小鼠显着延迟，并减少狼疮肾炎的发病率高达12个月的年龄，几乎所有的对照小鼠的时间已开发严重的肾小球肾炎。值得注意的是，致病性Th细胞在这些抗gp 39治疗的小鼠中保持完整，但它们的B细胞甚至在治疗后9个月也不能产生致病性自身抗体。我们的研究表明，在关键的时间窗口阻断致病性Th细胞上的gp 39与狼疮B细胞上的CD 40之间的相互作用，可以延迟自身免疫记忆B细胞的扩增，从而产生长期的治疗益处。
We investigated the role of gp39-CD40 interaction in the development of glomerulonephritis in lupus mice. In contrast to normal mice, lupus mice had much higher percentages of intensely gp39+ T cells in their spleens even at the preautoimmune age of 1 mo, and the further increase in gp39 expression by anti-CD3 Ab stimulation was markedly greater in lupus T cells. The pathogenic autoantibody-inducing ability of Th clones and splenic Th cells from lupus mice could be blocked in vitro by anti-gp39 Ab. Acceleration of lupus nephritis by the transfer of pathogenic autoantibody-inducing Th clones in vivo could also be completely blocked by anti-gp39 Ab. Surprisingly, a brief treatment of lupus mice with anti-gp39 Ab had a sustained beneficial effect on their spontaneous disease long after the Ab had been cleared from their systems. Only three injections of anti-gp39 Ab given to prenephritic lupus mice at 3 mo of age markedly delayed and reduced the incidence of lupus nephritis up to 12 mo of age by which time almost all the control mice had developed severe glomerulonephritis. Remarkably, pathogenic Th cells were left intact in these anti-gp39-treated mice but their B cells could not produce pathogenic autoantibodies even 9 mo after the therapy. Our studies suggest that blocking the interaction between gp39 on pathogenic Th cells and CD40 on lupus B cells at a crucial window of time delays the expansion autoimmune memory B cells resulting in long-term therapeutic benefits.