Study of graft-infiltrating cells in the rat small bowel allograft using FK-506 or FTY-720

背景：为了阐明新型高效免疫抑制剂FTY-720在小肠移植（SBTx）中的细胞机制，我们研究了移植物浸润细胞中的淋巴细胞亚群。材料和方法：异位SBTx在完全错配的DA （RT1a）和LOW （RT11）大鼠菌株组合中进行。接受者分为两组：氧化石墨烯无免疫抑制剂组（n=5），氧化石墨烯FTY-720治疗组（1mg/kg/天，第0天至第5天口服）（n=5）。第6天采集移植物浸润细胞，用流式细胞仪检测淋巴细胞亚群；WE/25（CD4；辅助性T细胞）、OX-8（CD8；细胞毒性T细胞）、OX- 39（CD25; IL-2R）、OX-33（CD45RA； B细胞）。结果：氧化石墨烯表现出典型的排斥组织学，而氧化石墨烯未表现出任何排斥迹象。以下数据差异有统计学意义：肠系膜淋巴结CD8阳性细胞（G0:21.2±4.3比G0:14.2±3.1%,p<0.05）、CD45RA阳性细胞（G0:38.1±7.9比G0:29.0±4.9%,p<0.05）；CD8阳性细胞（GO:28.1±7.6 us G0:12.8±3.7%,p<0.01）、CD25阳性细胞（GO: 5.1±1.6 us G0:2.3±1.7%,p<0.05）、CD45RA阳性细胞（GO:20.6±6.9 us GO:71.4±5.4%,p<0.01）；上皮内淋巴细胞CD4阳性细胞（GO:18.6±4.4 us G0:25.5±0.9%,p<0.01）、CDS阳性细胞（G0:59.1±9.2 us G0:34.0±12.2%,p<0.01）；CD4阳性细胞占G0:44.9±3.5比65.7±8.4%,p<0.01)， CDS阳性细胞占G0:32.9±3.4比G0:14。（4±1.7%,p<0.01）， CD25阳性细胞（G0:5.1±3.0,G0:1.0±0.7%,p<0.05）， CD45RA阳性细胞（G0:9.7±1.8,G0:2.5±0.3%,p<0.01）。结论：FTY-720对SBTx的免疫抑制作用可能与细胞毒性T细胞和IL-2R的消耗有关。移植物浸润细胞呈阳性。

Background: To elucidate the cellular mechanism of FTY-720, a new potent immunosuppressant, in small bowel transplantation (SBTx), we studied lymphocyte sub populations in graft infiltrating cells.Materials and methods : Heterotopic SBTx was performed in a fully mismatched DA (RT1a) to LOW (RT11) rat strain combination. Recipients were divided into two groups : GO) no immunosuppressant(n=5), GO) FTY-720 treatment (1mg/kg/day, oral garage from day 0 to day 5)(n=5). The graft infiltrating cells were harvested on day 6 and lymphocyte sub populations were analyzed by flow cytornetry with the following monoclonal antibodies ; WE/25(CD4 ; helper T cell), OX-8(CD8 ; cytotoxic T cell), OX- 39(CD25 ; IL-2R), and OX-33(CD45RA ; B cells).Results : GO demonstrated typical histology of rejection, while GO did not show any signs of rejection. The following data showed significant difference : CD8 positive cells (G0:21.2±4.3 us G0:14.2±3.1 %, p<0.05), CD45RA positive cells (G0:38.1±7.9 us G0:29.0±4.9 %, p<0.05) in the mesenteric lymph nodes ; CD8 positive cells (GO:28.1±7.6 us G0:12.8±3.7 %, p<0.01), CD25 positive cells (G0:5.1±1.6 us G0:2.3±1.7 %, p<0.05), CD45RA positive cells (GO:20.6±6.9 us GO:71.4±5.4 %, <0.01) in the pyres patches ; CD4 positive cells (GO:18.6±4.4 us G0:25.5±0.9 %, p<0.01), CDS positive cells (G0:59.1±9.2 us G0:34.0±12.2 %, p<0.01) in the intraepithelial lymphocytes ; CD4 positive cells (G0:44.9±3.5 us 65.7±8.4 %, p<0.01), CDS positive cells (G0:32.9±3.4 us G0:14. 4±1.7 %, p<0.01), CD25 positivecells (G0:5.1±3.0 us G0:1.0±0.7 %, p<0.05), CD45RA positive cells (G0:9.7±1,8 us G0:2.5±0,3 %, p<0.01) in the lamina propria lymphocytes.Conclusion: The immunosuppressive effect of FTY-720 in SBTx may be due to the depletion of cytotoxic T cells and IL-2R.positive cells in the graft infiltrating cells.