Dekel B, Marcus H, Herzel B H, Böcher W O, Passwell J H, Reisner Y
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Transplantation. 2000 Apr 15;69(7):1470-8. doi: 10.1097/00007890-200004150-00044.
We have recently demonstrated that human fetal renal tissue, implanted under the kidney capsule of severe immunodeficient rats, escapes early destruction by intraperitoneal infusion of allogeneic human peripheral blood mononuclear cells, compared with the rapid rejection of implants of human adult kidney tissue. Variable amounts of human mononuclear infiltrates were seen in the transplanted fetal kidney, however, prolonged survival of the fetal tissue (maintenance of graft architecture and significant growth) was independent of the cellular infiltrate.
We have used this experimental model to sequentially analyze transcript levels of interferon-gamma and interleukin (IL)-2 (T helper 1 cytokines), IL-4 and IL-10 (T helper 2 cytokines), RANTES, MIP1beta (beta chemokines) and their receptor CCR5, and Fas ligand (cytolytic effector molecule). Analysis was performed by reverse transcriptase-polymerase chain reaction, in both fetal and adult kidney grafts, after infusion of allogeneic human peripheral blood mononuclear cells.
Transcript levels of interferon-gamma and IL-2 in the fetal grafts were markedly reduced throughout follow-up, compared with those observed in the adult implants. Peak levels of these cytokines appeared late in the rejection process. Concomitant with these findings, IL-4 mRNA was up-regulated during the early phase, whereas IL-10 mRNA persisted throughout the rejection process, indicating that a T helper 2 bias occurred in the fetal grafts. In addition, RANTES (after an early peak), MIP1beta, CCR5, and Fas ligand mRNA levels were suppressed in the fetal grafts compared with those in the adult grafts.
These findings indicate that the immune response of kidney rejection is dependent on whether the target organ is of fetal or adult origin, and suggest that an allogeneic immune system mounts a T helper 2-biased response when the target organ is of fetal origin.
我们最近证明，与人类成人肾组织植入物的快速排斥相比，将人类胎儿肾组织植入严重免疫缺陷大鼠的肾被膜下，通过腹腔内输注同种异体人类外周血单个核细胞可避免早期破坏。然而，在移植的胎儿肾脏中可见不同数量的人类单核细胞浸润，胎儿组织的长期存活（移植物结构的维持和显著生长）与细胞浸润无关。
我们使用这个实验模型，在输注同种异体人类外周血单个核细胞后，通过逆转录聚合酶链反应，对胎儿和成人肾移植物中干扰素-γ、白细胞介素（IL）-2（辅助性T细胞1细胞因子）、IL-4和IL-10（辅助性T细胞2细胞因子）、调节激活正常T细胞表达和分泌的趋化因子（RANTES）、巨噬细胞炎性蛋白1β（β趋化因子）及其受体CCR5以及Fas配体（溶细胞效应分子）的转录水平进行了顺序分析。
与成人植入物中观察到的情况相比，在整个随访过程中，胎儿移植物中干扰素-γ和IL-2的转录水平显著降低。这些细胞因子的峰值水平在排斥过程后期出现。与这些发现同时出现的是，IL-4 mRNA在早期阶段上调，而IL-10 mRNA在整个排斥过程中持续存在，表明胎儿移植物中出现了辅助性T细胞2偏向。此外，与成人移植物相比，胎儿移植物中RANTES（在早期峰值后）、MIP1β、CCR5和Fas配体mRNA水平受到抑制。
这些发现表明，肾排斥的免疫反应取决于靶器官是胎儿来源还是成人来源，并提示当靶器官是胎儿来源时，同种异体免疫系统会产生辅助性T细胞2偏向的反应。
