Martinez O M, Villanueva J C, Lake J, Roberts J P, Ascher N L, Krams S M
Department of Surgery, University of California, San Francisco 94143.
Transplantation. 1993 May;55(5):1159-66. doi: 10.1097/00007890-199305000-00042.
IL-2 and IL-5 gene expression in response to alloantigen was studied in liver allograft recipients and in an in vitro system. Seventy-seven sequential liver allograft biopsies from 22 patients were analyzed for IL-2 and IL-5 mRNA by polymerase chain reaction and Southern blot hybridization. Message for IL-5 was present in 74% of allografts with rejection, 46% of allografts with resolving rejection, and 33% of allografts with no evidence of rejection. The frequency of IL-5 transcripts in rejecting allografts was significantly different than the frequency of IL-5 transcripts in grafts without evidence of rejection (P = 0.003). Message for IL-2 was detected in 29% of rejecting allografts, 18% of allografts without evidence of rejection, and 43% of allografts with resolving rejection. There was no significant association between IL-2 gene expression and the histopathological status of the allograft. Interestingly, 9 of 15 biopsies that contained IL-2 message in the no rejection and resolving rejection categories went on to display rejection shortly thereafter. IL-2 and IL-5 gene expression rarely occurred simultaneously within allografts. An in vitro system consisting of irradiated, allogeneic stimulator cells and normal peripheral blood mononuclear cells as responders was established to further investigate alloantigen-driven IL-2 and IL-5 production. Both IL-2 and IL-5 were produced in response to alloantigen as determined by specific bioassays. Maximal levels of IL-5 activity in culture supernatants generally followed maximal IL-2 levels by 24 hr, but both IL-2 and IL-5 production were dramatically inhibited by CsA. Analysis of cytokine gene expression revealed that IL-2 transcription peaked within the initial 24 hr of culture, whereas IL-5 transcription was maximal at 120 hr of culture. The expression of a CTL-specific serine esterase gene was similar to IL-5 in that it was maximal during the latter phases of the culture period. Thus, both human IL-2 and IL-5 are produced in response to alloantigen and are inhibitable by CsA. These data suggest that IL-2 and IL-5 may participate in cellular pathways of tissue damage within the rejecting allograft.
在肝移植受者和体外系统中研究了白细胞介素 -2（IL -2）和白细胞介素 -5（IL -5）基因对同种异体抗原的反应。通过聚合酶链反应和Southern印迹杂交分析了22例患者的77次连续肝移植活检组织中的IL -2和IL -5信使核糖核酸（mRNA）。在74%有排斥反应的同种异体移植物、46%排斥反应正在消退的同种异体移植物以及33%无排斥反应迹象的同种异体移植物中检测到了IL -5信使。有排斥反应的同种异体移植物中IL -5转录本的频率与无排斥反应迹象的移植物中IL -5转录本的频率有显著差异（P = 0.003）。在29%有排斥反应的同种异体移植物、18%无排斥反应迹象的同种异体移植物以及43%排斥反应正在消退的同种异体移植物中检测到了IL -2信使。IL -2基因表达与同种异体移植物的组织病理学状态之间无显著关联。有趣的是，在无排斥反应和排斥反应正在消退类别中含有IL -2信使的15份活检组织中有9份随后不久出现了排斥反应。IL -2和IL -5基因表达在同种异体移植物中很少同时发生。建立了一个由经照射的同种异体刺激细胞和正常外周血单个核细胞作为反应细胞的体外系统，以进一步研究同种异体抗原驱动的IL -2和IL -5产生。通过特异性生物测定法确定，IL -2和IL -5均是对同种异体抗原产生反应而产生的。培养上清液中IL -5活性的最高水平通常在IL -2最高水平出现24小时后出现，但IL -2和IL -5的产生均受到环孢素A（CsA）的显著抑制。细胞因子基因表达分析显示，IL -2转录在培养的最初24小时内达到峰值，而IL -5转录在培养120小时时达到最大值。细胞毒性T淋巴细胞（CTL）特异性丝氨酸酯酶基因的表达与IL -5相似，即在培养后期达到最大值。因此，人IL -2和IL -5均是对同种异体抗原产生反应而产生的，且可被CsA抑制。这些数据表明，IL -2和IL -5可能参与了正在发生排斥反应同种异体移植物中组织损伤的细胞途径。
