Oluwole S F, Engelstad K, Hardy M A
Department of Surgery, Columbia University College of Physicians and Surgeons, New York, New York 10032.
Cell Immunol. 1989 Nov;124(1):28-37. doi: 10.1016/0008-8749(89)90109-3.
In this study, cellular requirements for rejection are examined by the use of adoptive transfer assays in the ACI to Lewis cardiac allograft model. The findings show that adoptive transfer of 1 x 10(8) spleen cells (SpL), 5 x 10(7) T-cells, and 2 x 10(7) helper T-cells (W3/25+) obtained from normal, nonsensitized donors restores acute ACI graft rejection in sublethally irradiated (750 rad) Lewis recipients. In contrast, reconstitution with 2 x 10(7) cytotoxic T-cells (0X8+) does not restore first-set graft rejection. Reconstitution of the irradiated recipients with either W3/25+ or 0X8+ T-cells obtained from specifically sensitized syngeneic donors resulted in acute rejection. The W3/25+ T-cell subset was significantly more potent (P less than 0.01) in effecting rejection on a per-cell basis. Adoptive transfer of SpL, T-cells, and 0X8+ T-cells obtained from sensitized rats led to accelerated cardiac allograft rejection in the naive secondary recipients while W3/25+ T-cells did not. This study suggests that although the W3/25+ T-cells alone have the capacity to initiate first-set graft rejection, both W3/25+ and 0X8+ subsets appear to be critical to the completion of rejection of heart allografts. We also examined the capacity of adoptively transferred B-cells from sensitized donors to influence graft rejection. Our findings suggest that while B-cells fail to restore the capacity for graft rejection in irradiated recipients, they can, however, present MHC antigens to the secondary naive host thus causing allosensitization which results in accelerated rejection of a subsequent graft.
在本研究中,通过在ACI到Lewis心脏同种异体移植模型中使用过继性转移试验来检测排斥反应的细胞需求。研究结果表明,从正常、未致敏供体获得的1×10⁸个脾细胞(SpL)、5×10⁷个T细胞和2×10⁷个辅助性T细胞(W3/25⁺)的过继性转移可恢复经亚致死剂量照射(750拉德)的Lewis受体中的急性ACI移植物排斥反应。相比之下,用2×10⁷个细胞毒性T细胞(OX8⁺)进行重建不能恢复初次移植物排斥反应。用从特异性致敏的同基因供体获得的W3/25⁺或OX8⁺ T细胞重建受照射的受体导致急性排斥反应。W3/25⁺ T细胞亚群在每个细胞基础上引起排斥反应的能力明显更强(P小于0.01)。从致敏大鼠获得的SpL、T细胞和OX8⁺ T细胞的过继性转移导致未致敏的二级受体中同种异体心脏移植排斥反应加速,而W3/25⁺ T细胞则不会。这项研究表明,虽然单独的W3/25⁺ T细胞有能力引发初次移植物排斥反应,但W3/25⁺和OX8⁺亚群似乎对心脏同种异体移植排斥反应的完成都至关重要。我们还检测了来自致敏供体的过继性转移B细胞影响移植物排斥反应 的能力。我们的研究结果表明,虽然B细胞不能恢复受照射受体的移植物排斥反应能力,但它们可以将MHC抗原呈递给二级未致敏宿主,从而引起同种异体致敏,导致随后移植物的排斥反应加速。