Anti-CD52 blocks EAE independent of PD-1 signals and promotes repopulation dominated by double-negative T cells and newly generated T and B cells.,European Journal of Immunology

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Anti-CD52 blocks EAE independent of PD-1 signals and promotes repopulation dominated by double-negative T cells and newly generated T and B cells.
European Journal of Immunology ( IF 4.5 ) Pub Date : 2020-05-10 , DOI: 10.1002/eji.201948288
Yohannes Haile _{1,

2} , Adeolu Adegoke _{1,

2} , Bahareh Laribi ₂ , Jiaxin Lin _{1,

2} , Colin C Anderson _{1,

2,

3}

Affiliation

Lymphocyte depletion using anti‐CD52 antibody effectively reduces relapses of multiple sclerosis (MS). To begin to understand what mechanisms might control this outcome, we examined the effect of a murine‐CD52‐specific mAb on the depletion and repopulation of immune cells in mice with experimental autoimmune encephalomyelitis (EAE), a model of MS. We tested whether the tolerance‐promoting receptor programmed cell death protein‐1 (PD‐1) is required for disease remission post anti‐CD52, and found that PD‐1‐deficient mice with a more severe EAE were nevertheless effectively treated with anti‐CD52. Anti‐CD52 increased the proportions of newly generated T cells and double‐negative (DN) T cells while reducing newly generated B cells; the latter effect being associated with a higher expression of CD52 by these cells. In the longer term, anti‐CD52 caused substantial increases in the proportion of newly generated lymphocytes and DN T cells in mice with EAE. Thus, the rapid repopulation of lymphocytes from central lymphoid organs post anti‐CD52 may limit further disease. Furthermore, these data identify DN T cells, a subset with immunoregulatory potential, as a significant hyperrepopulating subset following CD52‐mediated depletion.

中文翻译：

抗CD52阻断独立于PD-1信号的EAE，并促进由双重阴性T细胞和新产生的T细胞和B细胞控制的再种群。

使用抗CD52抗体清除淋巴细胞可有效减少多发性硬化症（MS）的复发。为了开始了解哪些机制可能控制这一结果，我们检查了鼠CD52特异性mAb对MS模型实验性自身免疫性脑脊髓炎（EAE）小鼠免疫细胞耗竭和繁殖的影响。我们测试了抗CD52后疾病缓解是否需要增强耐受性的受体编程性细胞死亡蛋白-1（PD-1），并发现仍然使用抗CD52。抗CD52增加了新生成的T细胞和双阴性（DN）T细胞的比例，同时减少了新生成的B细胞。后者的作用与这些细胞CD52的较高表达有关。从长远来看，抗CD52导致EAE小鼠新产生的淋巴细胞和DN T细胞的比例大幅增加。因此，抗CD52后来自中央淋巴器官的淋巴细胞的快速繁殖可能会限制进一步的疾病。此外，这些数据将DN T细胞（具有免疫调节潜能的一个子集）识别为CD52介导的耗竭后的一个重要的过度繁殖子集。

更新日期：2020-05-10

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