Primed macrophages directly and specifically reject allografts
Primed macrophages directly and specifically reject allografts
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直接引发巨噬细胞并特异性排斥同种异体移植物
DOI：
10.1038/s41423-019-0226-0
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发表时间：
2020-03-01
影响因子：
24.1
通讯作者：
Zhao, Yong
中科院分区：
文献类型：
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作者：
Chu, Zhulang;Sun, Chenming;Zhao, Yong
单核细胞和巨噬细胞长期以来与急性和慢性同种异体移植物排斥有关;这是由它们促进炎症、通过抗体依赖性细胞毒性杀死靶细胞和调节适应性免疫的能力介导的。我们目前的研究表明，同种异体抗原引发的巨噬细胞过继转移到MHC匹配的免疫缺陷小鼠后，对皮肤移植物产生了特异性的急性排斥反应。致敏的巨噬细胞排斥同种异体移植物的能力基本上需要CD 4（+）T细胞的帮助，而不需要CD 8（+）T细胞的帮助。此外，与WT巨噬细胞相比，引发的穿孔素缺陷型巨噬细胞以显著延迟的模式排斥皮肤移植物，表明引发的巨噬细胞的穿孔素途径可能参与排斥过程。因此，在对同种异体移植物的免疫应答期间，在CD 4（+）T细胞的帮助下，引发的巨噬细胞被赋予了适应性免疫样特征，例如特异性。本研究挑战了我们对巨噬细胞功能的传统观点，并强调了巨噬细胞在哺乳动物先天免疫之外的生物学功能。
Monocytes and macrophages have long been associated with acute and chronic allograft rejection; this is mediated by their abilities to promote inflammation, kill target cells via antibody-dependent cytotoxicity and modulate adaptive immunity. Our present study showed that allogeneic antigen-primed macrophages acutely rejected skin grafts with specificity after adoptive transfer into MHC-matched immunodeficient mice. The ability of primed macrophages to reject allografts essentially requires the help of CD4(+) T cells and does not require the help of CD8(+) T cells. Moreover, the primed, perforin-deficient macrophages rejected the skin grafts in a significantly delayed pattern compared with WT macrophages, indicating that the perforin pathway of the primed macrophages is likely involved in the rejection process. Thus, primed macrophages are endowed with adaptive immunity-like features, such as specificity, with the help of CD4(+) T cells during the immune response to allografts. The present study challenges our traditional views of macrophage functions and highlights the biological functions of macrophages beyond innate immunity in mammals.