Recently, a novel humanized mouse model for systemic sclerosis (SSc) was established by transferring peripheral blood mononuclear cells (PBMC) from patients with SSc to Rag2−/−Il2rg−/− immunodeficient mice. Here, we aimed to investigate the role of T and B cells in this humanized mouse model. T and B cells were depleted in vitro from freshly isolated PBMC using anti-CD3 and anti-CD19 magnetic microbeads, respectively. Subsequently, PBMC and T or B cell-depleted PBMC were transferred into Rag2−/−/Il2rg−/− mice via intraperitoneal injection. Twelve weeks after the transfer, mice were sacrificed and evaluated. Mice transferred with whole PBMC from SSc patients developed systemic inflammation in the lungs, kidneys, and liver, and 6 out of 11 mice died or had to be sacrificed during the experiment. By contrast, such inflammation and death were not observed in mice transferred with corresponding T or B cell-depleted PBMC. In line with this finding, transfer with whole PBMC restored the splenic white pulp composing of human T, B, and plasma cells and led to the production of a considerable amount of human autoantibodies in recipient mice, while those immunological features were rarely observed in mice that received T or B cell-depleted PBMC. In contrast to our previous findings demonstrating a transfer of the protective effect of a B cell therapy into the mouse, treatment of SSc patients with chemical immunosuppressive drugs did not affect the pathogenicity of PBMC. This study demonstrates that both T and B cells are indispensable for the pathogenesis of the PBMC transfer-induced mouse model for SSc.

中文翻译：

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T 细胞和 B 细胞对于 PBMC 转移诱导的 SSc 人源化小鼠模型的开发都是不可或缺的


最近，通过将系统性硬化症（SSc）患者的外周血单核细胞（PBMC）转移到 Rag2−/−Il2rg−/− 免疫缺陷小鼠中，建立了一种新型的系统性硬化症（SSc）人源化小鼠模型。在这里，我们旨在研究 T 细胞和 B 细胞在这种人源化小鼠模型中的作用。分别使用抗 CD3 和抗 CD19 磁微珠在体外从新鲜分离的 PBMC 中去除 T 细胞和 B 细胞。随后，通过腹膜内注射将PBMC和T细胞或B细胞耗尽的PBMC转移至Rag2−/−/Il2rg−/−小鼠中。转移后十二周，处死小鼠并进行评估。移植了来自 SSc 患者的完整 PBMC 的小鼠出现了肺部、肾脏和肝脏的全身炎症，实验期间 11 只小鼠中有 6 只死亡或不得不被处死。相比之下，在用相应的 T 或 B 细胞耗尽的 PBMC 移植的小鼠中没有观察到这种炎症和死亡。与这一发现一致的是，全PBMC移植恢复了由人T细胞、B细胞和浆细胞组成的脾白髓，并导致受体小鼠产生大量人自身抗体，而这些免疫学特征在小鼠中很少观察到接受 T 或 B 细胞耗尽的 PBMC。与我们之前证明 B 细胞疗法的保护作用转移到小鼠体内的研究结果相反，用化学免疫抑制药物治疗 SSc 患者并不影响 PBMC 的致病性。这项研究表明，T 细胞和 B 细胞对于 PBMC 转移诱导的 SSc 小鼠模型的发病机制都是不可或缺的。