Levay-Young B, Shearer J D, Gruessner A C, Kim S C, Nahkleh R E, Gruessner R W G
Department of Surgery, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Transplant Proc. 2004 Mar;36(2):399-400. doi: 10.1016/j.transproceed.2004.01.086.
Immunomodulation by portal vein delivery of donor antigen reduces intestinal graft rejection. We investigated the impact of portal venous donor-specific cell augmentation (blood versus bone marrow) on cytokine expression in intestinal grafts versus native livers.
Ten groups of intestinal transplants (brown Norway male to Lewis female rats) varied by (1). the type of donor-specific cell augmentation and (2). the use and dose of tacrolimus-based immunosuppression. Tissue samples for histologic analysis and cytokine mRNA analysis were obtained at designated time points.
Without immunosuppression, no type of cell augmentation reduced the rate of rejection. With immunosuppression, outcome was significantly better after portal donor-specific blood transfusion (versus bone marrow infusion). Irrespective of the type of cell augmentation, severe rejection caused strong intragraft expression of IL-1alpha, IL-1beta, IFN-gamma, and TNF-alpha; liver expression mainly involved TNF-alpha. Of note, nonimmunosuppressed, cell-augmented rats showed hardly any differences in cytokine expression in their grafts versus significant increases in their native livers. With immunosuppression, bone marrow infusion (versus blood transfusion) increased intragraft cytokine expression of IL-1alpha, IL-1beta, IFN-gamma, as well as TNF-alpha, and liver expression of IL-1beta.
(1). Rejection and donor-specific cell augmentation independently caused differences in intragraft versus native liver cytokine expression after intestinal transplants. (2). Portal donor-specific blood transfusion (versus bone marrow infusion) lowered the incidence of rejection and diminished intragraft cytokine up-regulation. (3). In our study, TNF-alpha appeared to be the cytokine most strongly associated with rejection.
通过门静脉输送供体抗原进行免疫调节可减少肠道移植排斥反应。我们研究了门静脉供体特异性细胞增强（血液与骨髓）对肠道移植与天然肝脏中细胞因子表达的影响。
十组肠道移植实验（棕色挪威雄性大鼠到刘易斯雌性大鼠）因以下因素而有所不同：（1）供体特异性细胞增强的类型；（2）基于他克莫司的免疫抑制的使用和剂量。在指定时间点获取用于组织学分析和细胞因子mRNA分析的组织样本。
在没有免疫抑制的情况下，任何类型的细胞增强都不能降低排斥率。在有免疫抑制的情况下，门静脉供体特异性输血（与骨髓输注相比）后的结果明显更好。无论细胞增强的类型如何，严重排斥都会导致移植物内白细胞介素-1α、白细胞介素-1β、干扰素-γ和肿瘤坏死因子-α的强烈表达；肝脏表达主要涉及肿瘤坏死因子-α。值得注意的是，未进行免疫抑制、细胞增强的大鼠其移植物中的细胞因子表达几乎没有差异，而其天然肝脏中的表达则显著增加。在有免疫抑制的情况下，骨髓输注（与输血相比）增加了移植物内白细胞介素-1α、白细胞介素-1β、干扰素-γ以及肿瘤坏死因子-α的细胞因子表达，以及肝脏中白细胞介素-1β的表达。
（1）排斥反应和供体特异性细胞增强分别导致肠道移植后移植物与天然肝脏中细胞因子表达的差异。（2）门静脉供体特异性输血（与骨髓输注相比）降低了排斥反应的发生率，并减少了移植物内细胞因子的上调。（3）在我们的研究中，肿瘤坏死因子-α似乎是与排斥反应最密切相关的细胞因子。
