Yoshimura N, Kahan B D
Transplantation. 1985 Dec;40(6):708-13. doi: 10.1097/00007890-198512000-00027.
Suppressor T cells were identified in situ within renal allografts of hosts rendered unresponsive by perioperative administration of donor histocompatibility antigen, which was extracted from donor spleen cells with 3M KCl, combined with cyclosporine (Ag-CsA). Infiltrating cells harvested from Buffalo (BUF, RT1b) renal allografts ten days after transplantation into Wistar-Furth (WFu, RT1u) rats treated with a single i.v. injection of 5 mg 3M KCl-extracted donor antigen (Ag) combined with a three day course of CsA inhibited the mixed lymphocyte culture (MLC) reaction between normal responder WFu and irradiated BUF cells (79.3% suppression, P less than 0.001), but not third-party Brown-Norway (BN, RT1n) stimulator cells (-5.4% suppression, NS). The suppressor effect was not due to cytolysis: the infiltrating cells did not lyse 51Cr-labeled concanavalin A (Con-A) blastoid BUF cells, as did the infiltrating cells from nonimmunosuppressed recipient allografts undergoing rejection responses toward BUF (49% specific cytolysis, E/T = 25), but not third-party BN, target cells five days after transplantation. The suppressor cells were nonadherent to plastic dishes and sensitive to monoclonal antibodies (Mab) W3/13 HLK (pan-T cells: % suppressor -17.9) or cytotoxic/suppressor cells with Mab OX-8 (-5.0% suppression), but not W3/25 (helper; 48.6% suppression, P less than 0.025). Moreover, adoptive transfer of 10(6) infiltrating cells from Ag-CsA-treated recipient allografts into virgin WFu hosts prolonged primary BUF graft survival from 7.2 to 14.0 days (P less than 0.05), but not third-party BN grafts (treated MST = 11.9 +/- 3.9 days versus untreated MST = 11.0 +/- 2.9 days, NS). On the other hand, infiltrating cells from CsA-only-treated recipient allografts could not transfer this effect (MST = 7.7 +/- 0.5 days, P less than 0.01). Finally, retransplantation of the BUF allograft from the Ag-CsA treated rat to a syngeneic, virgin WFu host ten days after primary transplantation yielded prolonged survival with MST 11.4 +/- 2.3 versus control primary graft survival in untreated animals of 7.2 +/- 0.6 days (P less than 0.001). BUF allografts from treated WFu hosts retransplanted into third-party BN rats did not display prolonged graft survival (MST = 9.2 +/- 1.1 days) compared with primary BUF grafts in untreated BN recipients (MST = 9.2 +/- 2.0 days, NS). The presence of suppressor T cells both in the spleen and in situ in renal allografts following Ag-CsA treatment suggests that local mechanisms may augment systemic elements to control the generation of alloimmunity.
通过围手术期给予从供体脾细胞中用3M KCl提取的供体组织相容性抗原并联合环孢素（Ag - CsA），使宿主对移植肾无反应，从而在其肾移植组织中原位鉴定出抑制性T细胞。将5mg 3M KCl提取的供体抗原（Ag）单次静脉注射并联合三天疗程的环孢素A（CsA）处理的Wistar - Furth（WFu，RT1u）大鼠，在移植水牛（BUF，RT1b）肾移植十天后收获浸润细胞，该浸润细胞抑制了正常反应性WFu与经辐照的BUF细胞之间的混合淋巴细胞培养（MLC）反应（抑制率79.3%，P小于0.001），但对第三方棕色挪威（BN，RT1n）刺激细胞无抑制作用（抑制率 - 5.4%，无显著性差异）。抑制作用并非由于细胞溶解：浸润细胞不像未免疫抑制的接受者同种异体移植组织中正在对BUF发生排斥反应的浸润细胞那样裂解51Cr标记的刀豆蛋白A（Con - A）母细胞样BUF细胞（49%特异性细胞溶解，效靶比 = 25），但移植五天后对第三方BN靶细胞无此作用。抑制性细胞不黏附于塑料培养皿，对单克隆抗体（Mab）W3/13 HLK（全T细胞：抑制率 - 17.9%）或针对细胞毒性/抑制性细胞的Mab OX - 8（抑制率 - 5.0%）敏感，但对W3/25（辅助性细胞；抑制率48.6%，P小于0.025）不敏感。此外，将10⁶个来自Ag - CsA处理的接受者同种异体移植组织的浸润细胞过继转移到未接触过抗原的WFu宿主中，可使原发性BUF移植物存活时间从7.2天延长至14.0天（P小于0.05），但对第三方BN移植物无此作用（处理后平均存活时间 = 11.9±3.9天，未处理平均存活时间 = 11.0±2.9天，无显著性差异）。另一方面，仅用CsA处理的接受者同种异体移植组织的浸润细胞不能传递这种效应（平均存活时间 = 7.7±0.5天，P小于0.01）。最后，在初次移植十天后，将来自Ag - CsA处理大鼠的BUF同种异体移植物再次移植到同基因、未接触过抗原的WFu宿主中，其存活时间延长，平均存活时间为11.4±2.3天，而未处理动物的对照原发性移植物存活时间为7.2±0.6天（P小于0.001）。将处理后的WFu宿主的BUF同种异体移植物再次移植到第三方BN大鼠中，与未处理的BN接受者中的原发性BUF移植物相比，未显示移植物存活时间延长（平均存活时间 = 9.2±1.1天）（平均存活时间 = 9.2±2.0天，无显著性差异）。Ag - CsA处理后，脾脏和肾移植组织原位均存在抑制性T细胞，这表明局部机制可能增强全身因素以控制同种免疫的产生。
