Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Department of Surgery, Division of HPB & Transplant Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Sci Rep. 2019 Apr 12;9(1):5984. doi: 10.1038/s41598-019-42401-9.
Tissue-resident memory T (T) cells are characterized by their surface expression of CD69 and can be subdivided in CD103+ and CD103- T cells. The origin and functional characteristics of T cells in the renal allograft are largely unknown. To determine these features we studied T cells in transplant nephrectomies. T cells with a CD103+ and CD103- phenotype were present in all samples (n = 13) and were mainly CD8+ T cells. Of note, donor-derived T cells were only detectable in renal allografts that failed in the first month after transplantation. Grafts, which failed later, mainly contained recipient derived T cells. The gene expression profiles of the recipient derived CD8+ T cells were studied in more detail and showed a previously described signature of tissue residence within both CD103+ and CD103- T cells. All CD8+ T cells had strong effector abilities through the production of IFNγ and TNFα, and harboured high levels of intracellular granzyme B and low levels of perforin. In conclusion, our results demonstrate that donor and recipient T cells reside in the rejected renal allograft. Over time, the donor-derived T cells are replaced by recipient T cells which have features that enables these cells to aggressively respond to the allograft.
组织驻留记忆 T(T)细胞的特征是其表面表达 CD69,并且可以细分为 CD103+和 CD103-T 细胞。肾移植中 T 细胞的起源和功能特征在很大程度上尚不清楚。为了确定这些特征,我们研究了移植肾切除术中的 T 细胞。所有样本(n=13)均存在具有 CD103+和 CD103-表型的 T 细胞,并且主要是 CD8+T 细胞。值得注意的是,在移植后第一个月内失败的肾移植中仅可检测到供体来源的 T 细胞。较晚失败的移植物主要包含受体来源的 T 细胞。我们更详细地研究了受体衍生的 CD8+T 细胞的基因表达谱,发现 CD103+和 CD103-T 细胞内均存在先前描述的组织驻留特征。所有 CD8+T 细胞均通过产生 IFNγ和 TNFα而具有强大的效应功能,并且具有高水平的细胞内颗粒酶 B 和低水平的穿孔素。总之,我们的研究结果表明,供体和受体 T 细胞存在于排斥的肾移植中。随着时间的推移,供体来源的 T 细胞被受体来源的 T 细胞取代,这些细胞具有使其能够积极响应移植的特征。