小肠移植急性排斥反应期移植肠白细胞介素2受体和细胞间粘附分子1的表达

目的　探讨移植肠白细胞介素２ 受体（ Ｉ Ｌ２ Ｒ） 和细胞间粘附分子１（ Ｉ Ｃ Ａ Ｍ１） 的表达在小肠移植排斥反应中的意义及诊断价值。方法　选用近交系大鼠 Ｆ３４４／ Ｎ 和 Ｗｉｓｔａｒ／ Ａ 进行全小肠异位移植,实验分４ 组,第１ 组： Ｗｉｓｔａｒ;第２ 组： Ｗｉｓｔａｒ→ Ｗｉｓｔａｒ ;第３ 组： Ｆ３４４ → Ｗｉｓｔａｒ;第４ 组： Ｆ３４４ → Ｗｉｓｔａｒ＋环孢霉素 Ａ（６ ｍｇ·ｋｇ － １·ｄ － １） 。术后第３ 、５ 、７ 天取各组动物移植肠标本进行病理学检查,应用免疫组化技术（ Ｓ Ｐ 法） 检测移植肠 Ｉ Ｌ２ Ｒ 和 Ｉ Ｃ Ａ Ｍ１ 的表达。结果　病理学检查显示第３ 组大鼠在术后第３ 、５ 、７天分别符合轻、中、重度排斥,第２ 、４ 组无明显排斥征象。第３ 组 Ｉ Ｌ２ Ｒ 表达在术后均非常显著高于其他３ 个对照组;第３ 组 Ｉ Ｃ Ａ Ｍ１ 表达在术后第３ 、５ 天较相似,尤其在上皮细胞表现为强阳性,并显著高于第１ 组。但第２ 、４ 对照组 Ｉ Ｃ Ａ Ｍ１ 表达也较高,第３ 组仅在术后第３ 天 Ｉ Ｃ Ａ Ｍ１ 评分显著高于第２ 组。结论　 Ｉ Ｌ２ Ｒ 和 Ｉ Ｃ Ａ Ｍ１ 阳性细胞在小肠移植排斥反应过程中发挥重要作用。应用单克隆抗体阻     

Interleukin-15 production during liver allograft rejection in humans

BACKGROUND: The activity of interleukin (IL)-15, a cytokine produced by macrophages, is similar to that of IL-2. We investigated whether IL-15 plays a role in liver allograft rejection. METHODS: We evaluated plasma levels and intrahepatic expression of IL-15 in 35 patients after liver transplantation, and then analyzed in vitro the influence of anticalcineurin drugs or steroids on IL-15 production and secretion. Finally, we examined the effects of IL-15 on lymphocyte proliferation in mixed lymphocyte culture in the presence or absence of anticalcineurin drugs or steroids. RESULTS: Plasma levels and in situ expression of IL-15 were enhanced during liver allograft rejection, particularly during steroid-resistant acute rejection and during chronic rejection. In vitro, IL-15 production and secretion were inhibited by neither anticalcineurin drugs nor steroids. Exogenous IL-15 enhanced cell-mediated immune response, and this effect was not inhibited by immunosuppressive drugs. CONCLUSIONS: IL-15 can play a role in the initiation and outcome of acute and chronic rejection. Anti-IL-15 therapy in combination with classic immunosuppression therapy might thus be beneficial in the prevention of acute, and especially chronic, allograft rejection.     

小肠移植排斥反应期移植肠粘膜细胞凋亡的研究

目的 明确移植肠上皮细胞凋亡在小肠移植排斥反应中的意义及诊断价值。方法 选用近交系大鼠Ｆ３４４／Ｎ和Ｗｉｓｔａｒ／Ａ进行全小肠异位移植,实验分４组。第１组：非基本对照 ;第２组;同基因移植组;第３组;异基因移植组;第４组;异基因移植加环孢霉素Ａ治疗组。术的第３、５、７天取移植肠进行病理学检查,采用ＴｄＴ介导的脱氧核苷酸原位末端标记法（ＴＵＮＥＬ）检测移植肠上皮细胞凋亡。结果 病理学检查显示第３组大     

Osteopontin expression in acute renal allograft rejection

BACKGROUND: Osteopontin (OPN) is a potent chemoattractant for mononuclear cells that is up-regulated in various inflammatory states of the kidney. The role of OPN and its expression in human renal allograft rejection are unknown. METHODS: We examined by immunohistochemistry and in situ hybridization, renal biopsies from patients with acute rejection (N= 22), protocol biopsies without rejection (N= 9), and perioperative donor biopsies (N= 35) for intrarenal expression of OPN, and its correlation with clinical, laboratory, and histopathologic parameters. In the rejection biopsies, interstitial monocyte/macrophage infiltration, tubulointerstitial cell proliferation/regeneration and apoptosis were investigated. RESULTS: In the majority of rejection biopsies, OPN expression by proximal tubular epithelium was widespread, and tended to be enhanced in the tubules surrounded by numerous inflammatory cells. Conversely, in patients that did not experience episodes of rejection and in donor biopsies, OPN expression by proximal tubules was nil or weak. OPN mRNA was colocalized with its translated protein in the renal tubular epithelium. OPN expression positively correlated with the degree of interstitial inflammation (P < 0.05), CD68+ monocyte infiltration (P < 0.01), Ki-67+ regenerating tubular and interstitial cells (P < 0.05 and P < 0.005, respectively), but not with terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL)-positive apoptotic tubular cells. CONCLUSION: These data suggest that inducible expression of OPN in the tubular epithelium may have a pathogenic role in acute renal allograft rejection by mediating interstitial monocyte infiltration and possibly tubular regeneration.     

Endotoxin in the peripheral blood during acute intestinal allograft rejection

Intestinal rejection is associated with increased gut permeability and bacterial translocation. The present study examined endotoxin and proinflammatory cytokines in the peripheral circulation during acute intestinal rejection. Heterotopic intestinal transplants were performed using Lewis rats (RT1¹) as donors and DA rats (RT1^a) as recipients. DA rats with intestinal isografts were used as controls. Serum samples were obtained at sacrifice on postoperative days (POD) 7 and 14. Lipopolysaccharide (LPS) was measured using the limulus amoebocyte lysate assay. Interleukin-1 (IL-1) and 6 (IL-6) and tumor necrosis factor- (TNF-) were measured using bioassays. Large amounts of LPS were detected in the serum of intestinal allograft recipients concurrent with the development of graft rejection. Serum IL-6 and TNF- levels were significantly elevated in the allograft recipients on both POD 7 and 14 when compared to DA isografts (P<0.05). Serum IL-1 activity was not detected in the allograft or isograft recipients at either of the two time points. Further studies are warranted to determine the role of intraluminal bacteria and their products in the pathophysiology of intestinal allograft rejection.     

Predominant expression of the Th2 response in chronic cardiac allograft rejection

Chronic rejection is the main cause of late allograft failure in patients. CD4+ T cells activated by indirect recognition of alloantigens are implicated in this rejection reaction. However, the type of T cell response (Th1 vs Th2) that contributes to chronic rejection has not been fully investigated. The purpose of this study is to examine whether chronic rejection is associated with a polarized T-cell response in a rat cardiac allograft model, where long-term graft survival is achieved by intrathymic immunomodulation with donor class I, RT1.Aa, allopeptides. All long-surviving allografts showed histological evidence of chronic rejection. Chronic rejection was associated with high levels of intragraft Th2 cytokines and the Th2-regulated alloantibodies. The Th2 response was systemic, since long-surviving allografts with chronic rejection had high levels of serum IL-10. The predominance of the Th2 cytokines demonstrates that the Th2 response was not sufficient for the prevention of chronic rejection in this model. The predominant expression of Th2 cytokines, together with the presence of Th2-regulated alloantibodies, suggests that the Th2 response may play a role in the development of chronic rejection.     

Detection of canine intestinal allograft rejection by in vivo electrophysiologic monitoring

The aim of this study was to evaluate the significance of in vivo measurements of electrophysiologic parameters for the detection of canine small bowel (SB) allograft rejection. In dogs of group I (n = 17) a heterotopic SB autotransplantation was performed. Dogs of group II (n = 8) received a heterotopic SB allograft in a fully mismatched donor-recipient combination. No immunosuppression was given. All grafts were monitored regularly by in vivo measurements of transepithelial potential differences (PDs) and by biopsies of the grafts. The overall technical failure rate was 36% caused by thrombosis at the vascular anastomosis in most cases. All successful autografts survived the experimental period and showed physiologic PD responses after stimulation by both a theophylline solution and a glucose solution. The successful allografts survived 5.5 +/- 0.2 days (mean +/- SEM); the transepithelial PDs showed normal responses at postoperative day 3, but showed decreased responses at day 5 (P less than 0.05) and reversed responses at day 6 (P less than 0.05). The diminished PD responses correlated well with the onset of histologic alterations characteristic of rejection. This study demonstrates that serial monitoring of transepithelial PD responses is a noninvasive method to detect acute SB allograft rejection.     

转录因子T-bet与GATA结合蛋白3的比值在大鼠肺移植急性排斥反应中的mRNA表达及其意义

目的 探讨T-bet(T-box expression in T cells)和GATA结合蛋白3(GATA-3)在大鼠肺移植急性排斥反应中的mRNA表达及其意义.方法 建立同种异体大鼠肺移植模型,实验分为正常对照组(n=5只)、同种异体移植3 d组(n=4只)和5 d组(n=6只),用实时荧光定量逆转录-聚合酶链反应(RT-PCR)法,检测移植后肺组织中T-bet和GATA-3的mRNA表达.结果 实时荧光定量RT-PCR检测T-bet和GATA-3的扩增效率为78%～85%,批内和批间实验循环阈值(Ct)变化均＜0.15.与止常对照和右侧非移植肺比较,同种异体移植术后3 d组,T-bet和GATA-3无显著性改变,但其比值明显高于右侧肺;同种异体移植术后5 d组,T-bet表达增高(9.31拷贝/106 18 S拷贝),但差异无统计学意义(P＞0.05),GATA-3表达下降(0.88拷贝/105 18 S拷贝),T-bet/GATA3的比值增高(1.12),差异均有统计学意义(P＜0.05).结论 实时荧光定量RT-PCR检测T-bet和GATA-3结果准确可靠.在急性排斥反应中,T-bet表达升高,GATA-3表达降低,其中GATA-3的表达起主导作用.T-bet/GATA-3的比值比单独检测T-bet或GATA-3更能客观地评价大鼠肺移植急性排斥反应.