Bartlett S T, Schweitzer E J, Kuo P C, Johnson L B, Delatorre A, Hadley G A
Department of Surgery, University of Maryland School of Medicine, Baltimore 21201, USA.
Transplantation. 1997 Jan 27;63(2):299-303. doi: 10.1097/00007890-199701270-00021.
The results of clinical islet transplantation have remained poor when compared with the consistent success of pancreas transplantation. Autoimmunity has usually been discounted as a cause of islet transplant failure. Previously, we demonstrated that pancreas transplants from the diabetes resistant BB rat (BB-DR) function indefinitely in autoimmune diabetic hosts, but islets from the same donor are vulnerable to recurrent autoimmunity. Addition of 100 million pancreatic lymph node cells (PLNC) to BB-DR islets restores resistance to autoimmunity and leads to repletion of a T cell subset (RT6.1) in the recipients. Autoimmune (BB-Ac) and streptozocin (BB-Sz) diabetic BB rats were recipients of Wistar Furth (WF) intraportal islet or islets plus PLNC transplants with cyclosporine 5 mg/kg/day recipient treatment. One cohort of Brown Norway (BN) islet transplants to BB-Ac with CsA was performed. At the termination of the experiment, recipient peripheral blood lymphocytes (PBL) were characterized by flow cytometry (FACS) for class I, CD4, CD8, RT6.1, and RT6.2, a T cell maturation marker found in WF but not BB rats. All (14/14) WF and 75% (6/8) BN islet transplants to BB-Ac recipients failed after a mean of 42 and 36 days, respectively, despite CsA immunosuppression. WF islets were successful in 6/8 (75%) transplants to BB-Sz recipients (P<0.001 vs. BB-Ac recipients), confirming that autoimmunity is the major cause of islet failure in BB-Ac rats. Addition of PLNC to WF islets increased the survival in BB-Ac to 82% (9/11) (P<0.0001 vs. WF islets alone). Recipients of islet+PLNC express 19.7% RT6.2 compared with 4.6% and 4.0% for WF islets alone in BB-Ac (P<0.01) and BB-Sz (P<0.01), respectively. Autoimmunity is an important factor leading to islet transplant failure in autoimmune diabetic BB rats. Addition of donor PLNC prevent islet allograft failure and leads to recipient chimerism for a donor T cell subset (RT6.2) associated with resistance to autoimmunity.
与胰腺移植的持续成功相比，临床胰岛移植的结果一直不佳。自身免疫通常被认为不是胰岛移植失败的原因。此前，我们证明，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宿主中能无限期发挥功能，但来自同一供体的胰岛易受复发性自身免疫的影响。向BB-DR胰岛中添加1亿个胰腺淋巴结细胞（PLNC）可恢复对自身免疫的抗性，并导致受体中一个T细胞亚群（RT6.1）的补充。自身免疫性（BB-Ac）和链脲佐菌素诱导的糖尿病（BB-Sz）BB大鼠接受了Wistar Furth（WF）门静脉内胰岛移植或胰岛加PLNC移植，并接受5mg/kg/天的环孢素受体治疗。进行了一组将Brown Norway（BN）胰岛移植到接受环孢素治疗的BB-Ac大鼠的实验。在实验结束时，通过流式细胞术（FACS）对受体外周血淋巴细胞（PBL）进行I类、CD4、CD8、RT6.1和RT6.2的表征，RT6.2是一种在WF大鼠而非BB大鼠中发现的T细胞成熟标志物。尽管有环孢素免疫抑制，所有（14/14）WF胰岛移植和75%（6/8）BN胰岛移植到BB-Ac受体后分别在平均42天和36天后失败。WF胰岛移植到BB-Sz受体中有6/8（75%）成功（与BB-Ac受体相比，P<0.001），证实自身免疫是BB-Ac大鼠胰岛移植失败的主要原因。向WF胰岛中添加PLNC可使BB-Ac受体中的存活率提高到82%（9/11）（与单独使用WF胰岛相比，P<0.0001）。胰岛+PLNC的受体表达19.7%的RT6.2，而单独使用WF胰岛在BB-Ac（P<0.01）和BB-Sz（P<0.01）中分别为4.6%和4.0%。自身免疫是导致自身免疫性糖尿病BB大鼠胰岛移植失败的重要因素。添加供体PLNC可防止胰岛同种异体移植失败，并导致受体出现与自身免疫抗性相关的供体T细胞亚群（RT6.2）的嵌合现象。
