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B cell depletion in murine lupus using cytotoxic T lymphocytes in vivo: Feasibility and benefit.
Cellular Immunology ( IF 4.3 ) Pub Date : 2020-05-05 , DOI: 10.1016/j.cellimm.2020.104117
Kateryna Soloviova 1 , Irina Puliaeva 1 , Maksym Puliaiev 1 , Roman Puliaev 1 , Charles S Via 1
Affiliation  

Given the promising results in human lupus with B cell depletion, we tested whether in vivo cytotoxic T lymphocyte (CTL) could eliminate autoreactive B cells in the setting of murine lupus. Using the parent-into-F1 (P → F1) model to generate CTL that eliminate B cells, we found that transfer ofNZB parental splenocytes into lupus-prone female NZB/W F1 mice resulted in profound B cell reduction whereas NZW → F1 mice exhibited defective B cell elimination. Using pre-disease or early disease B/W mice as hosts, NZB → F1 mice exhibited B cell depletion and improved proteinuria but no improvement in survival whereas NZW → F1 mice had significantly reduced proteinuria and prolonged survival. Thus, despite the defective IL-2 environment in B/W F1 mice, generation of CTL and B cell depletion is feasible in NZB → F1 mice. The surprising increase in survival for NZW → F1 mice despite defective B cell elimination suggests that NZW splenocytes may contain a beneficial down regulatory cell.

中文翻译:

在体内使用细胞毒性T淋巴细胞消除鼠科狼疮中的B细胞:可行性和益处。

鉴于具有B细胞耗竭的人类狼疮的有希望的结果,我们测试了体内细胞毒性T淋巴细胞(CTL)是否可以消除鼠狼疮中的自身反应性B细胞。使用亲代F1(P→F1)模型生成消除B细胞的CTL,我们发现将NZB亲本脾细胞转移至易患狼疮的雌性NZB / W F1小鼠会导致B细胞大量减少,而NZW→F1小鼠表现出B细胞消除缺陷。使用疾病前或早期疾病的B / W小鼠作为宿主,NZB→F1小鼠表现出B细胞耗竭并改善了蛋白尿,但未改善存活率,而NZW→F1小鼠则显着降低了蛋白尿并延长了生存期。因此,尽管B / W F1小鼠的IL-2环境存在缺陷,但在NZB→F1小鼠中CTL和B细胞耗竭的产生还是可行的。
更新日期:2020-05-05
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