CD8 T cell-mediated rejection of intestinal allografts is resistant to inhibition of the CD40/CD154 costimulatory pathway

BACKGROUND: Disruption of the CD40/CD154 pathway inhibits rejection in numerous models. The importance of this pathway on intestinal allograft rejection was examined in this study. METHODS: Intestinal grafts from B6C3F1 mice transplanted into C57BL/6 recipients were assessed histologically for rejection. RESULTS: The monoclonal antibody to CD154, MR1, failed to inhibit rejection in wild-type mice. Similarly, CD154-/- recipient mice rejected intestinal allografts. MR1 did inhibit early rejection in CD8-/- mice, but had no effect in CD4-/- recipients. All MR1-treated CD8-/- recipients eventually developed rejection. No benefit was observed when blockade of the CD40/CD154 pathway by MR1 was combined with blockade of the CD28/B7 pathway by mCTLA4Ig. CONCLUSIONS: These data suggest that CD4+ T cells mediating intestinal allograft rejection may be more dependent upon the CD40/CD154 pathway than CD8+ T cells. This finding highlights the importance of identifying agents that suppress CD8+ T cell-mediated rejection.     

外科危重病人的营养支持

目的：总结外科危重病人应用肠外营养与肠内支持的方法及经验。方法：应用肠内营养（EN）支持26例,全部通过鼻肠管滴入安素或爱伦多溶液,通过中心静脉营养（CV－TPN）70例,周围静脉肠外营养（PV－TPN）52例,均应用3升营养袋匀速滴入全合一营养液（TNA）。结果：26例全胃切除术后病人应用EN,无死亡及其他严重并发症,应用TPN组有3例死亡,死亡原因与TPN无直接关系,病人恢复快,平均住院天数缩短。结论：由于外科危重病人存在独特的代谢特点,大部分病人存在营养不良,故营养支持对外科危重病人至关重要,直接影响病人的康得和预后,因此对外科危重病人应该进行积极的营养支持治疗。     

股外侧肌上端肌支股骨骨（膜）瓣的解剖与临床应用

目的报道股外侧肌上端肌支股骨骨(膜)瓣的应用解剖及临床应用。方法在40侧成人下肢标本上解剖观测股外侧肌上端血管肌支的分支分布情况,设计以股外侧肌支为蒂的股骨骨(膜)瓣移位术,并进行了摹拟手术。1989年2月～1999年2月,以股外侧肌支为蒂切取股骨骨(膜)瓣移位修复股骨上段骨不连、骨缺损7例。结果股外侧肌上端肌支来自旋股外侧动脉横支,肌支在大转子尖下(16.8±3.0)cm发出肌骨膜支和骨膜支,肌骨膜支外径1.4～1.7mm,长度2.7～5.6cm,骨膜支外径0.4～0.6mm,长度1.2～1.5cm。骨膜血管向下或水平走行,达骨膜后发出吻合支,参与形成股骨血管网,分布于股骨上段。临床应用的7例,术后经18～42个月的随访,骨折于术后10～18周获得骨性愈合。髋关节活动度在180°者4例,120°者2例,65°者1例。供区愈合良好,无不适。结论以股外侧肌上端肌支为蒂的股骨骨(膜)瓣,可用于修复股骨中上段的骨不连、骨缺损。     

肝癌最佳肿瘤标记物及相关指标群的研究

目的：探讨肝癌的最佳标记组合。方法：收集肝癌病人45例和62例健康成人,检测AFP、ERBB-2、IL-2R等27种指标,计算各指标的特异性、阳性预期值、敏感性、阴性预期值、总有效率,及上述5项的平均值。结果：平均值排序前6位的是：TPA、GGT、AFP、FU、AKP、PU;选取AFP=FU、TPA三标记物的敏感性达97.06%,其中前二基的敏感性为92.70%,三项中任一项阳性所致的特异性为63.68%。结论：AFP、FU、TPA是检测肝癌的最佳指标组合。多指标联合检测较单指标检测有更高的特异性的敏感性。     

雅胆子油乳诱导膀胱癌BIU—87细胞凋亡的研究

目的：研究雅胆子油乳对膀胱癌细胞的作用。探讨其抑制膀胱癌的机制。方法：将5ul/ml雅胆子油乳作用于人BIU-87膀胱癌细胞,利用流式细胞仪和透射电子显微镜分析和观察作用结果。结果：鸦胆子油乳阻止ＢＩＵ-87膀胱癌细胞由G0/G1周期进入S期,并诱导人BIU-87膀胱癌细胞的凋亡。结论：鸭胆子油乳抗癌作用机制之一是诱导人BIU-87膀胱癌细胞的凋亡。     

急性颈椎损伤MRI表现与脊髓损伤的相关性

目的　探讨MRI检查在判断急性颈椎损伤患者脊髓损伤程度中的作用。方法　对 82例急性颈椎损伤患者在受伤 2 4h内行MRI检查 ,并进行早期连续的临床检查 ,分析MRI表现与脊髓损伤程度之间的相关性。结果　急性颈椎损伤的 10种MRI表现中 ,髓内出血提示完全性脊髓损伤 (FrankelA级 ) ;脊髓肿胀及脊髓水肿多见于FrankelA -C级的病人 ,同时 ,脊髓肿胀及水肿的程度与脊髓损伤程度成正比 ;脊髓受压多见于FrankelA级和FrankelB级的患者 ;颈椎脱位多见于脊髓损伤程度较重 (FrankelA -C级 )的患者 ;椎管狭窄与脊髓损伤程度之间无明确相关性 ,但多见于老年患者 ;颈椎间盘突出、颈椎椎体骨折、颈椎附件骨折及韧带损伤与脊髓损伤程度间无明显相关性。结论　急性颈椎损伤患者早期行MRI检查 ,可以帮助判断脊髓损伤的程度 ,对治疗方法的选择及准确判断预后具有重要的指导意义。     

Ex Vivo-Expanded Natural CD4+CD25+ Regulatory T Cells Synergize With Host T-Cell Depletion to Promote Long-Term Survival of Allografts

Foxp3⁺CD4⁺CD25⁺ natural regulatory T (nT_reg) cells have been shown in immunodeficient mice to suppress allograft rejection after adoptive cotransfer. We hypothesized that immunotherapy using ex vivo -expanded nT_reg could suppress allograft rejection in wild-type mice. Donor alloantigen (alloAg) specificity of naive splenic nT_reg was enriched in vitro by culturing with anti-CD3/CD28-coated Dynabeads plus bone marrow-derived dendritic cells (BM-DC) in the presence of interleukin (IL)-2 or IL-2 plus transforming growth factor (TGF)-β. On average, 96.2% fresh CD4⁺CD25⁺ nT_reg were intracellular Foxp3⁺. By d+20 in culture, 6.4% nT_reg were Foxp3⁺ following expansion with IL-2 alone, and 14.4% or 19.7% nT_reg were Foxp3⁺ when expanded with IL-2 plus 0.5 or 2.5 ng/mL TGF-β, respectively. In vitro , alloAg-enriched, TGF-β/IL-2-conditioned nT_reg exerted stronger donor alloAg-specific suppression than cells with IL-2 alone in mixed lymphocyte reaction (MLR) assays. In vivo , alloAg-enriched, TGF-β/IL-2-conditioned nT_reg expressed high-level Foxp3 following infusion, effectively overcame acute rejection and induced long-term survival of donor but not third-party heart allografts in peritransplant host T-cell-depleted mice. Long-term surviving allografts were noted to possess Foxp3⁺ graft-infiltrating cells of exogenous and endogenous origins. In conjunction with transient host T-cell depletion, therapeutic use of ex vivo -expanded nT_reg may be a practical means of preventing acute allograft rejection.     

Unaltered Graft Survival and Intragraft Lymphocytes Infiltration in the Cardiac Allograft of Cxcr3−/- Mouse Recipients

Previous studies showed that absence of chemokine receptor Cxcr3 or its blockade prolong mouse cardiac allograft survival. We evaluated the effect of the CXCR3 receptor antagonist MRL-957 on cardiac allograft survival, and also examined the impact of anti-CXCR3 mAb in human CXCR3 knock-in mice. We found only a moderate increase in graft survival (10.5 and 16.6 days, p < 0.05) using either the antagonist or the antibody, respectively, compared to control (8.7 days). We re-evaluated cardiac allograft survival with two different lines of Cxcr3^−/- mice. Interestingly, in our hands, neither of the independently derived Cxcr3^−/- lines showed remarkable prolongation, with mean graft survival of 9.5 and 10.8 days, respectively. There was no difference in the number of infiltrating mononuclear cells, expansion of splenic T cells or IFN-γ production of alloreactive T cells. Mechanistically, an increased other chemokine receptor fraction in the graft infiltrating CD8 T cells in Cxcr3^−/- recipients compared to wild-type recipients suggested compensatory T-cell trafficking in the absence of Cxcr3. We conclude Cxcr3 may contribute to, but does not govern, leukocyte trafficking in this transplant model.