Induction of fonor specific unresponsiveness by pre-operative administraton of donor antigen in combination with a short course of cyclosporine in rat allogeneic kidney transplantation.

本文观察了环孢素（CsA）三天疗程与氯化钾（KCl）提取的供者输血抗原一次静脉注射联合应用对大鼠同种异体肾移植的免疫抑制作用。在Wistar-Furth（WF）大鼠中，连续3天单独给予10 mg/Kg/天CsA可略微延长布法罗（BUF）肾移植物的存活时间，从7天延长至11天。CsA与供体抗原或供体输血的组合在移植前一天给药，导致更大的供体特异性延长移植物存活。移植后10天，接受CaA和供体抗原联合治疗的受者淋巴细胞不仅在MLR中对供体刺激细胞表现出特异性不应答，而且特异性抑制vergin WF应答细胞对供体BUF刺激细胞的增殖反应。此外，抑制细胞的活性被完全照射的BUF大鼠的腘淋巴结中的局部GVHR反应减弱所取代，而不是在第三方Brown Norway大鼠中，以及全身过继转移后BUF肾同种异体移植物存活的延长所取代。给予低剂量环磷酰胺降低了延长移植物存活的能力。以10天为间隔的两个额外的CSA治疗周期，试图维持T抑制细胞对T辅助细胞的优势，将移植物存活的中位数延长至65天。使用供体输血没有实现类似的延长。这些结果表明，供体抗原amilifies特定的抑制细胞的诱导和CsA促进抑制细胞优势的建立，导致宿主无反应性。

The immunosuppressive effect of the combination of a therr day coures of cyclosporine (CsA) with one i.v. injection of 3 mol KCL extracted donor antigen of donor blood transfusion was tested on rat allogeneic kidney transplantation. Administration of 10 mg/Kg/day CsA alone for three days slightly prolonged Buffalo (BUF) kidney allograft survival time from 7 to 11 days in Wistar-Furth (WF) rats. The combination of CsA with donor antigen or with donor blood transfusion administered one day prior to transplantation caused greater donor specific prolongation of graft survival. Lymphocytes harvested from recipient 10 days after transplantation that had received combined therapy with CaA and donor antigen not only displayed specific unrsponsiveness to donor stimulator cells in MLR but also specifically suppressed the proliferative response of vergin WF responder cell to donor BUF stimulator cells. Furthermore suppressor cell activeity was subbgested by diminished responses of local GVHR in popliteal lymph nodes of totally irraddiated BUF rats, but not in those of third party Brown Norway rats, and by prolongation of BUF kinney allograft survival following systemic adoptive transfer. Administeration of low dosw cyclophosphamide reduced the capacity to prolong graft survival. Two additionla cycles of CSA therapy at 10-day intervals administered in an attempt to maintain T suppressor dominance over T helper cell prolonged median graft survival to 65 days. Similar prolongation was not achieved using donor blood transfusion. These findings suggest that donor antigen amlifies the induction of specific suppressor cells and CsA facilitates the establishment of suppressor cell dominance, leading to host unresponsiveness.