Table_1_Long-Term Signs of T Cell and Myeloid Cell Activation After Intestinal Transplantation With Cellular Rejections Contributing to Further Increase of CD16+ Cell Subsets.pdf

The intestine mediates a delicate balance between tolerogenic and inflammatory immune responses. The continuous pathogen encounter might also augment immune cell responses contributing to complications observed upon intestinal transplantation (ITx). We thus hypothesized that ITx patients show persistent signs of immune cell activation affecting both the adaptive and innate immune cell compartment. Information on the impact of intestinal grafts on immune cell composition, however, especially in the long-term is sparse. We here assessed activated and differentiated adaptive and innate immune subsets according to time, previous experience of cellular or antibody-mediated rejections or type of transplant after ITx applying multi-parametric flow cytometry, gene expression, serum cytokine and chemokine profiling. ITx patients showed an increase in CD16 expressing monocytes and myeloid dendritic cells (DCs) compared to healthy controls. This was even detectable in patients who were transplanted more than 10 years ago. Also, conventional CD4+ and CD8+ T cells showed persistent signs of activation counterbalanced by increased activated CCR4+ regulatory T cells. Patients with previous cellular rejections had even higher proportions of CD16+ monocytes and DCs, whereas transplanting higher donor mass with multi-visceral grafts was associated with increased T cell activation. The persistent inflammation and innate immune cell activation might contribute to unsatisfactory results after ITx.

肠道在调节致耐受性免疫反应与炎症性免疫反应之间维持着一种微妙的平衡。持续的病原体遭遇可能还会增强免疫细胞反应，从而加剧在肠道移植（ITx）过程中观察到的并发症。因此，我们假设ITx患者表现出持续的免疫细胞活化迹象，影响适应性免疫细胞和固有免疫细胞区室。然而，关于肠道移植对免疫细胞组成的影响，尤其是长期影响的信息却十分匮乏。在本研究中，我们根据时间、细胞或抗体介导的排斥史以及移植类型，运用多参数流式细胞术、基因表达、血清细胞因子和趋化因子分析，评估了ITx患者中活化与分化的适应性免疫和固有免疫亚群。与健康对照组相比，ITx患者CD16表达的单核细胞和髓系树突状细胞（DCs）的数量增加，这一变化甚至可在移植超过10年的患者中观察到。此外，常规CD4+和CD8+ T细胞显示出持续的活化迹象，这种迹象通过增加活化的CCR4+调节性T细胞得到平衡。既往有细胞排斥史的患者，其CD16+单核细胞和DCs的比例更高，而移植较大供体体积的多器官移植与T细胞活化的增加相关。持续的炎症和固有免疫细胞活化可能对ITx后的不满意结果产生贡献。