Yoshimura N, Kahan B D
Transplantation. 1985 Oct;40(4):384-9. doi: 10.1097/00007890-198510000-00008.
Systemic adoptive transfer was employed to assess the immunosuppressive efficacy of antigen-specific suppressor T (Ts) cells purified from recipients treated with 3M KCl-extracted donor histocompatibility antigen (Ag) and cyclosporine (CsA). Suppressor cells were obtained from Wistar-Furth (WFu, RT-1u) hosts treated with a single i.v. injection of 5 mg 3M KCl-extracted donor Buffalo (Buf, RT-1b) antigen combined with a three-day course of CsA, a group that displays prolonged renal allograft survival (MST 23.2 +/- 10.2 days) compared with animals treated with CsA alone (MST 12.2 +/- 2.4 days). These noncytolytic, OX-8 phenotype, 800-rad-resistant/1500-rad-sensitive, nylon-wool-nonadherent and cyclophosphamide-sensitive suppressor T cells (1 X 10(6)) were adoptively transferred ten days after transplantation into virgin, secondary syngeneic hosts-thereby prolonging Buf graft survival from 7.2 to 17.5 days. The suppressor effect was immunologically specific; adoptive transfer did not prolong the survival of third-party Brown-Norway (BN) grafts (MST 10.4 +/- 3.1 days) compared with the nontreated control group (MST 11.0 +/- 2.9 days). The potency of Ts cells purified from Ag-CsA-treated hosts to transfer unresponsiveness into normal secondary WFu hosts (MST 17.5 +/- 8.0 days) was stronger than that of Ts cells from hosts treated with CsA only (MST 10.6 +/- 2.6 days). Moreover, in vitro stimulation of monoclonal-antibody-purified Ts cells by irradiated donor Buf spleen cells potentiated the in vivo induced suppressor activity, leading to an MST of 38.1 +/- 32.6 days; indeed 3 of 12 animals (25%) displayed permanent unresponsiveness. Furthermore, Ts cells from Ag-CsA-treated hosts displayed a synergistic effect with a three-day course of CsA administration into the secondary hosts (MST 24.2 +/- 8.0 days) compared with animals only treated with CsA (MST 12.2 +/- 2.4 days, P less than 0.001). Moreover, the combination of the Ag-CsA regimen with Ts cells administered one day after transplantation caused even greater prolongation of graft survival (MST 34.2 +/- 14.2 days) compared with Ag-CsA-treated hosts (MST 23.2 +/- 10.2 days, P less than 0.025). Thus adoptively transferred antigen-specific suppressor T cells may be explored to intensify the specific immunosuppressive effect of the Ag-CsA regimen to achieve long-term unresponsiveness.
采用全身过继性转移法评估从接受3M KCl提取的供体组织相容性抗原（Ag）和环孢素（CsA）治疗的受体中纯化得到的抗原特异性抑制性T（Ts）细胞的免疫抑制效果。抑制性细胞取自经静脉单次注射5 mg 3M KCl提取的供体布法罗（Buf，RT-1b）抗原并联合三天疗程CsA治疗的Wistar-Furth（WFu，RT-1u）宿主，与仅用CsA治疗的动物（平均存活时间12.2±2.4天）相比，该组动物的肾移植存活时间延长（平均存活时间23.2±10.2天）。这些非细胞溶解性、OX-8表型、800拉德抗性/1500拉德敏感性、尼龙毛非黏附性且对环磷酰胺敏感的抑制性T细胞（1×10⁶个）在移植后十天过继性转移至初次、同基因二级宿主，从而使Buf移植物存活时间从7.2天延长至17.5天。抑制作用具有免疫特异性；与未治疗的对照组（平均存活时间11.0±2.9天）相比，过继性转移并未延长第三方棕色挪威（BN）移植物的存活时间（平均存活时间10.4±3.1天）。从Ag-CsA治疗的宿主中纯化得到的Ts细胞将无反应性转移至正常二级WFu宿主（平均存活时间17.5±8.0天）的能力强于仅用CsA治疗的宿主来源的Ts细胞（平均存活时间10.6±2.6天）。此外，经照射的供体Buf脾细胞对单克隆抗体纯化的Ts细胞进行体外刺激可增强体内诱导的抑制活性，使平均存活时间达到38.1±32.6天；实际上，12只动物中有3只（25%）表现出永久性无反应性。此外，与仅用CsA治疗的动物（平均存活时间12.2±2.4天，P<0.001）相比，来自Ag-CsA治疗宿主的Ts细胞与在二级宿主中给予三天疗程的CsA具有协同作用（平均存活时间24.2±8.0天）。此外，与Ag-CsA治疗的宿主（平均存活时间23.2±10.2天，P<0.025）相比，在移植后一天给予Ag-CsA方案与Ts细胞联合治疗可使移植物存活时间延长更多（平均存活时间34.2±14.2天）。因此，可探索过继性转移的抗原特异性抑制性T细胞以增强Ag-CsA方案的特异性免疫抑制效果，从而实现长期无反应性。
