Wright J R, Hauptfeld V, Lacy P E
Hospital for Children, Department of Pathology, Dalhousie University Faculty of Medicine, Nova Scotia, Canada.
Am J Pathol. 1989 Feb;134(2):237-42.
Aberrant Ia antigen expression has been implicated in the pathogenesis of type 1 diabetes. Ia antigen expression was induced on isolated B10.BR murine islet parenchymal cells by culturing them for 5 days with lymphokine supernatants containing interferon-gamma (IFN-gamma) or with recombinant murine IFN-gamma + recombinant tumor necrosis factor. Ia positivity was confirmed by indirect immunofluorescence. Islets cultured for 5 days without cytokines were Ia-negative. Purified B10.BR islets allografted into the portal veins of C57BL/6J mice do not reject, which allowed the authors to determine whether aberrant expression of Ia on parenchymal cells has a deleterious effect on allograft survival. Ia-positive or Ia-negative islets were transplanted via the portal vein into diabetic C57BL/6J mice. All mice remained normoglycemic until they were killed at 30 to 60 days. Well-granulated islet allografts were identified histologically in all mice. The experiment was repeated using Balb/cJ mice as donors. Purified Balb/cJ islets are rapidly rejected by C57BL/6J mice. Induction of Ia expression on Balb/cJ islets significantly improved allograft survival. These findings indicate that Ia-positive islet cells do not induce rejection in these allograft models but may actually have a protective effect.
异常的Ia抗原表达与1型糖尿病的发病机制有关。通过将分离的B10.BR小鼠胰岛实质细胞与含有γ干扰素（IFN-γ）的淋巴因子上清液或与重组小鼠IFN-γ+重组肿瘤坏死因子一起培养5天，可诱导其Ia抗原表达。通过间接免疫荧光法确认Ia阳性。在无细胞因子的情况下培养5天的胰岛为Ia阴性。纯化的B10.BR胰岛移植到C57BL/6J小鼠的门静脉中不会被排斥，这使得作者能够确定实质细胞上Ia的异常表达是否对同种异体移植存活有有害影响。将Ia阳性或Ia阴性胰岛通过门静脉移植到糖尿病C57BL/6J小鼠体内。所有小鼠在30至60天被处死前均保持血糖正常。组织学检查在所有小鼠中均发现了胰岛移植组织良好。使用Balb/cJ小鼠作为供体重复该实验。纯化的Balb/cJ胰岛会被C57BL/6J小鼠迅速排斥。诱导Balb/cJ胰岛表达Ia可显著提高同种异体移植的存活率。这些发现表明，Ia阳性胰岛细胞在这些同种异体移植模型中不会诱导排斥反应，反而可能具有保护作用。
