Center for Vascularized Composite Allotransplantation, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Division of Surgery and Interventional Science, University College London, London, United Kingdom; St Andrew's Center for Burns and Plastic Surgery, Chelmsford, United Kingdom.
Mol Immunol. 2018 Jul;99:53-65. doi: 10.1016/j.molimm.2018.04.004. Epub 2018 Apr 23.
B lymphocyte-induced maturation protein 1 (Blimp-1) transcription factor is expressed in multiple cell lineages and in particular, T cells. However, the role of Blimp-1 in T cell-mediated allograft tolerance is still unknown.
This study is the first to investigate transplanted skin allograft survival using transgenic (Tg) mice with T cell overexpression of Blimp-1.
Without any immunosuppression, fully MHC-mismatched skin allografts on Tg(+) mice had a significantly prolonged survival rate and partial tolerance at 90 days. Allograft lymphocytic infiltration was decreased in Tg(+) mice and a dampened donor-stimulated alloimmune response was seen. An absolute cell number ratio of inflammatory Th1 and Th17 cells against anti-inflammatory regulatory T (Treg) and IL-10-producing T cells, as well as cytolytic proteins, were significantly decreased in lymphoid organs and allograft. Blimp-1 transgenic T cells displayed an increased Treg differentiation capability and enhanced suppression of T cell proliferation. Overexpression of Blimp-1 in T cells promoted the formation of an anti-inflammatory cell-cytokine composition, both systemically and locally via transcription factor modulation such as T-bet downregulation and FoxP3 upregulation.
As such, allograft survival was made possible due to Th1 suppression and Treg amplification with the creation of an 'allograft protective microenvironment'.
B 淋巴细胞诱导成熟蛋白 1（Blimp-1）转录因子在多种细胞谱系中表达，特别是在 T 细胞中。然而，Blimp-1 在 T 细胞介导的同种异体移植耐受中的作用尚不清楚。
本研究首次使用 T 细胞过表达 Blimp-1 的转基因（Tg）小鼠来研究移植皮肤同种异体移植物的存活。
在没有任何免疫抑制的情况下，Tg(+) 小鼠上的完全 MHC 错配皮肤同种异体移植物的存活率显著延长，在 90 天时出现部分耐受。Tg(+) 小鼠中的同种异体淋巴细胞浸润减少，并且观察到供体刺激的同种免疫反应减弱。在淋巴器官和同种异体移植物中，炎症性 Th1 和 Th17 细胞与抗炎调节性 T（Treg）和产生 IL-10 的 T 细胞以及细胞毒性蛋白的绝对细胞数比值显著降低。Blimp-1 转基因 T 细胞显示出增加的 Treg 分化能力和增强的 T 细胞增殖抑制作用。T 细胞中 Blimp-1 的过表达通过转录因子调节（如 T-bet 下调和 FoxP3 上调）促进全身性和局部抗炎细胞因子组成的形成，从而实现同种异体移植物的存活。
因此，由于 Th1 抑制和 Treg 扩增，形成了“同种异体保护微环境”，从而实现了同种异体移植物的存活。
