Bartlett S T, Chin T, Dirden B, Quereshi A, Hadley G
Department of Surgery, University of Maryland Medical System, Baltimore, USA.
Surgery. 1995 Aug;118(2):392-7; discussion 397-8. doi: 10.1016/s0039-6060(05)80350-2.
Recurrent autoimmune beta-cell destruction may contribute to the poor results of clinical islet transplantation. Pancreas transplants from diabetes-resistant BB rats (BB-DR) are uniformly successful in autoimmune diabetic BB rats (BB-Ac), but isolated islets are destroyed, despite immunosuppression. In this study we tested the hypothesis that whole pancreas transplants abrogate autoimmunity by passive transfer to the host of an autoregulatory T-cell subset.
BB-Ac rats served as recipients of BB-DR or Wistar Furth (WF) pancreas or islet transplants. Two cohorts of islet transplants included 50 or 100 x 10(6) peripancreatic lymph node cells (LNCs). Recipients were monitored for recurrent diabetes and subjected to fluorescence-activated cell sorter analysis of peripheral blood lymphocytes after 200 days by using monoclonal antibodies to class I, CD4, CD8, RT6.2, and RT6.1.
BB-DR pancreas transplants replete the RT6.1+ T-cell subset in BB-Ac rats, whereas BB-DR islet transplants, which are susceptible to recurrent autoimmunity, do not. Addition of 100 x 10(6) LNC results in repletion of RT6.1 to the same degree as the whole pancreas and leads to complete protection of the islets. WF pancreas transplants result in the appearance of RT6.2+ T cells in BB-Ac recipients, an RT allele that BB rats lack.
BB-Ac rat recipients of whole pancreatic or islets plus LNCs transplants become chimeric for a donor T-cell population that prevents recurrent autoimmune diabetes. Deliberate inclusion of donor lymphoid cells with clinical islet transplants may be beneficial.
复发性自身免疫性β细胞破坏可能导致临床胰岛移植效果不佳。来自糖尿病抗性BB大鼠（BB-DR）的胰腺移植在自身免疫性糖尿病BB大鼠（BB-Ac）中均成功，但尽管进行了免疫抑制，分离的胰岛仍会被破坏。在本研究中，我们测试了以下假设：全胰腺移植通过将自身调节性T细胞亚群被动转移至宿主来消除自身免疫。
BB-Ac大鼠作为接受BB-DR或Wistar Furth（WF）胰腺或胰岛移植的受体。两组胰岛移植分别包含50或100×10⁶个胰腺周围淋巴结细胞（LNC）。监测受体是否复发糖尿病，并在200天后使用针对I类、CD4、CD8、RT6.2和RT6.1的单克隆抗体对其外周血淋巴细胞进行荧光激活细胞分选分析。
BB-DR胰腺移植可使BB-Ac大鼠中的RT6.1⁺ T细胞亚群得以补充，而易发生复发性自身免疫的BB-DR胰岛移植则不能。添加100×10⁶个LNC可使RT6.1的补充程度与全胰腺相同，并导致胰岛得到完全保护。WF胰腺移植导致BB-Ac受体中出现RT6.2⁺ T细胞，RT是BB大鼠所缺乏的一个等位基因。
接受全胰腺或胰岛加LNC移植的BB-Ac大鼠受体对于能够预防复发性自身免疫性糖尿病的供体T细胞群体而言成为了嵌合体。在临床胰岛移植中有意加入供体淋巴细胞可能有益。
