Donor IL-6 deficiency evidently reduces memory T cell responses in sensitized transplant recipients
Donor IL-6 deficiency evidently reduces memory T cell responses in sensitized transplant recipients
复制标题
供体 IL-6 缺乏明显降低了致敏移植受者的记忆 T 细胞反应。
DOI：
10.1016/j.trim.2018.09.005
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发表时间：
2018-12-01
影响因子：
1.5
通讯作者：
Gong, Weihua
中科院分区：
文献类型：
--
作者：
Chen, Juntao;Liu, Chen;Gong, Weihua
背景：致敏移植耐受诱导的主要原因是记忆T细胞的产生。目前尚不清楚移植物生态位的改变(如促炎细胞因子水平)是否会影响记忆T细胞的产生。方法：将IL6缺陷或野生型(WT)C57BL/6心脏移植物移植到预致敏野生型Bale/c受体。结果：供者IL6缺乏可显著延长致敏同种异体移植物的存活时间。与WT组相比，IL6KO组移植后第3天外周血中效应记忆CD4+T细胞(CD4+CD44+CD62L-)的频率显著降低(p=0.026)。IL 6 KO组移植后第3天外周血中CD8+CD8+T细胞(CD8+CD44+CD62L-)的比例显著低于WT组(P<0.0 0 1)。中枢记忆T细胞各组间差异无统计学意义。组织学结果显示，供体致炎细胞因子IL6缺乏组(IL6KO组)保留了心脏的结构，淋巴细胞轻度浸润，而野生型供体(对照组)则导致移植物心肌纤维内明显的淋巴细胞浸润和心脏结构的破坏。结论：供体移植物缺乏促炎细胞因子可以有效地延长致敏移植物的存活，其原因是外周记忆T细胞而不是中枢记忆T细胞显著减少。这一靶向IL6信号通路的机制可能为预防致敏移植受者的同种异体排斥反应提供新的视角。
Background: Resistance of tolerance induction in sensitized transplantation is mainly caused by generation of memory T cells. It is unknown whether alteration of graft niche such as level of pro-inflammatory cytokines can affect generation of memory T cells.Methods: IL6 deficient or wildtype (WT) C57BL/6 heart grafts were transplanted into pre-sensitized wildtype BALE/c recipients. Frequencies of memory T cells in the peripheral blood, grafts, and spleen were evaluated.Results: We revealed that deficiency of donor IL6 could significant prolong sensitized allograft survival. Compared with counterpart of WT group, frequency of effector memory CD4 + T cells (CD4 + CD44 + CD62L-) in the peripheral blood was significantly lower in the IL6 KO group (p = .026) at day 3 post-transplantation. Frequency of effector memory CD8 + T cells (CD8 + CD44 + CD62L-) in the peripheral blood was significantly lower in the IL6 KO group (p < .0001) at day 3 post-transplant in comparison to that of WT group. No significant difference of central memory T cells was found between these groups. Histology demonstrated that deficiency of donor pro-inflammatory cytokine IL6 (IL6 KO group) preserved cardiac architecture with a mild infiltration of lymphocytes, whereas wildtype donor (control group) caused an evident lymphocytic infiltration within myocardial fibers of grafts and destruction of cardiac structure.Conclusion: Deficiency of proinflammatory IL6 of donor graft could effectively prolong sensitized allograft survival, which was caused by a remarkable decrease of peripheral memory T cells rather than central memory T cells. This unveiled mechanism of targeting IL6 signaling pathway might provide a novel insight into preventing allograft rejection for sensitized transplant recipients.