Fuchimoto Y, Yamada K, Shimizu A, Yasumoto A, Sawada T, Huang C H, Sachs D H
Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA.
J Immunol. 1999 May 15;162(10):5704-11.
The persistence of donor leukocytes in recipients of organ allografts has been associated with long-term graft acceptance. However, it remains unclear whether this peripheral donor cell microchimerism plays an active role in graft acceptance or is simply a consequence of the maintenance of sufficient immunosuppression to avoid rejection. A model of kidney transplantation between swine leukocyte Ag (SLA)-matched miniature swine, in which tolerance can be established with or without immunosuppressive treatment, has been used to study the correlation between donor leukocyte chimerism and kidney graft acceptance. SLA-identical kidney transplants were performed from animals positive for an allelic pig leukocyte Ag to animals negative for this marker. SLA-identical kidney transplant recipients given a 12-day course of cyclosporine (CyA) (n = 3) became tolerant, showing stable serum creatinine levels (1-2 mg/dl) after cessation of CyA treatment. Donor cell chimerism (0.2-0.7%) was present by FACS in all three animals with peak levels detected at 3 wk. Two control animals receiving SLA-identical kidney grafts without CyA also showed stable serum creatinine levels and became tolerant. However, in neither of these animals could donor leukocytes be detected in the peripheral blood beyond 1 wk following transplantation. In one additional control animal, ureteral obstruction occurred at day 10, and was associated with additional peripheral chimerism, presumably related to inflammation rather than to immune status. These results indicate that the persistence of donor cell chimerism is not a requirement for the maintenance of tolerance to organ allografts in this model.
供体白细胞在器官移植受者体内的持续存在与长期移植接受相关。然而，目前尚不清楚这种外周供体细胞微嵌合体在移植接受中是发挥积极作用，还是仅仅是维持足够免疫抑制以避免排斥反应的结果。一种猪白细胞抗原（SLA）匹配的小型猪之间的肾移植模型已被用于研究供体白细胞嵌合体与肾移植接受之间的相关性，在该模型中，无论有无免疫抑制治疗都可以建立耐受性。从等位基因猪白细胞抗原阳性的动物向该标志物阴性的动物进行SLA相同的肾移植。接受12天环孢素（CyA）疗程（n = 3）的SLA相同肾移植受者变得耐受，在停止CyA治疗后血清肌酐水平稳定（1 - 2mg/dl）。通过流式细胞术在所有三只动物中均检测到供体细胞嵌合体（0.2 - 0.7%），在3周时检测到峰值水平。另外两只接受SLA相同肾移植但未接受CyA的对照动物也显示出血清肌酐水平稳定并变得耐受。然而，在这两只动物中，移植后1周以上在外周血中均未检测到供体白细胞。在另一只对照动物中，在第10天发生输尿管梗阻，并伴有额外的外周嵌合体，推测与炎症而非免疫状态有关。这些结果表明，在该模型中，供体细胞嵌合体的持续存在不是维持对器官移植耐受性的必要条件。
