Pearce N W, Spinelli A, Gurley K E, Hall B M
Division of Nephrology, Stanford University School of Medicine, California 94305-5114.
Transplantation. 1993 Feb;55(2):374-80. doi: 10.1097/00007890-199302000-00027.
CD4+ cells from CsA-treated DA rats with long-surviving PVG heart allografts specifically suppress the capacity of naive CD4+ cells to restore allograft rejection in irradiated DA rats, but have normal donor-specific alloreactivity in MLC. CD4+ suppressor cells from CsA-treated DA rats cultured for 3 days against either PVG or DA spleen cells lost the capacity to transfer suppression into irradiated DA rats grafted with PVG hearts and regained the ability to mediate rejection. However, these cells retained suppressor function when stimulated with donor-specific alloantigen in media supplemented with 20% Con A supernatant. CD4+ cells from CsA-treated rats cultured against either third-party stimulator cells or syngeneic cells expressing anti-PVG idiotype in media supplemented with Con A supernatant failed to maintain suppressor cell function. CD4+ cells from CsA-treated rats cultured in media supplemented with Con A supernatant alone also failed to maintain suppressor function. Suppressor cell function in culture was not maintained by rIL-2. mAb to the IL-2 receptor alpha chain (CD25) prevented the maintenance of suppressor cell function in media supplemented with Con A supernatant. Con A supernatant is rich in IFN-gamma, but addition of an anti-IFN-gamma mAb to the culture did not affect the maintenance of suppressor cells. These studies demonstrate that the CD4+ suppressor cell from CsA-treated rats with long-surviving grafts is short-lived; its survival is dependent upon contact with specific alloantigens and cytokines, one of which is IL-2. In the absence of cytokines and/or specific alloantigen, the CD4+ cells regain the capacity to initiate graft rejection in irradiated rats, suggesting that within the CD4+ subpopulation there is a fragile balance between cells with the capacity to suppress and effect rejection.
来自长期存活PVG心脏同种异体移植的环孢素处理的DA大鼠的CD4 +细胞特异性抑制幼稚CD4 +细胞在受辐照DA大鼠中恢复同种异体移植排斥的能力，但在混合淋巴细胞培养中具有正常的供体特异性同种异体反应性。用PVG或DA脾细胞培养3天的环孢素处理的DA大鼠的CD4 +抑制细胞失去了将抑制作用转移到移植有PVG心脏的受辐照DA大鼠中的能力，并恢复了介导排斥反应的能力。然而，当在补充有20％刀豆蛋白A上清液的培养基中用供体特异性同种异体抗原刺激时，这些细胞保留了抑制功能。在补充有刀豆蛋白A上清液的培养基中，用第三方刺激细胞或表达抗PVG独特型的同基因细胞培养的环孢素处理大鼠的CD4 +细胞未能维持抑制细胞功能。仅在补充有刀豆蛋白A上清液的培养基中培养的环孢素处理大鼠的CD4 +细胞也未能维持抑制功能。培养中的抑制细胞功能不能由重组白细胞介素-2维持。抗白细胞介素-2受体α链（CD25）单克隆抗体阻止了在补充有刀豆蛋白A上清液的培养基中抑制细胞功能的维持。刀豆蛋白A上清液富含干扰素-γ，但向培养物中添加抗干扰素-γ单克隆抗体不影响抑制细胞的维持。这些研究表明，来自长期存活移植物的环孢素处理大鼠的CD4 +抑制细胞寿命短暂；其存活取决于与特定同种异体抗原和细胞因子的接触，其中之一是白细胞介素-2。在没有细胞因子和/或特定同种异体抗原的情况下，CD4 +细胞恢复了在受辐照大鼠中引发移植排斥的能力，这表明在CD4 +亚群内，具有抑制和效应排斥能力的细胞之间存在脆弱的平衡。
