Bradley J A, Sarawar S R, Porteous C, Wood P J, Cård S, Ager A, Bolton E M, Bell E B
University Department of Surgery, Western Infirmary, Glasgow, Scotland.
Transplantation. 1992 Feb;53(2):477-82. doi: 10.1097/00007890-199202010-00040.
PVG-rnu/rnu nude rats reject fully allogenic renal (DA) and skin (BN, AO) allografts after the adoptive transfer of naive CD4+ T cells alone, but rejection is accompanied by the accumulation of many nude-derived CD8+ leukocytes within the graft. In addition, mononuclear cells infiltrating the rejecting renal grafts in these animals display cytotoxic activity in vitro against specific and third-party alloantigens. In this investigation we have treated CD4+ T cell-restored nude rats bearing renal or skin allografts with the mAb MRC OX8 to deplete the host of CD8+ cells. In vivo treatment with OX8 completely eliminated CD8+ cells from rejecting grafts of both kidney and skin, but it did not prevent graft rejection, nor did OX8 treatment abolish the cytotoxic effector cells found in nude rat spleen or in graft-infiltrating cells (GIC) of rejecting renal allografts. The nature of the cytotoxic activity was examined with anti-CD3 mAb 1F4, which was shown to block conventional CD8+ Tc killing in vitro but did not inhibit allogeneic target cell lysis by spleen cells from nude rats. The cytotoxic activity found in GIC of rejecting allografts was not inhibited by anti-CD3 mAb, suggesting that these cytotoxic effector cells were CD3-CD8- and were of extrathymic origin. We conclude that non-thymus-derived CD8+ GIC are not essential for allograft rejection in CD4+ T cell-restored nude rats.
PVG-rnu/rnu裸鼠在单独过继转移未致敏的CD4⁺ T细胞后，能完全排斥同种异体肾（DA）和皮肤（BN、AO）移植，但排斥反应伴随着许多裸鼠来源的CD8⁺白细胞在移植物内的积聚。此外，浸润这些动物正在排斥的肾移植的单核细胞在体外对特异性和第三方同种异体抗原表现出细胞毒性活性。在本研究中，我们用单克隆抗体MRC OX8处理了携带肾或皮肤同种异体移植的CD4⁺ T细胞恢复的裸鼠，以清除宿主中的CD8⁺细胞。用OX8进行体内治疗完全消除了肾和皮肤排斥移植物中的CD8⁺细胞，但它并没有阻止移植物排斥，OX8治疗也没有消除在裸鼠脾脏或正在排斥的肾移植的移植物浸润细胞（GIC）中发现的细胞毒性效应细胞。用抗CD3单克隆抗体1F4检测细胞毒性活性的性质，结果表明该抗体在体外可阻断传统的CD8⁺ Tc杀伤，但不抑制裸鼠脾脏细胞对同种异体靶细胞的裂解。在排斥移植物的GIC中发现的细胞毒性活性不受抗CD3单克隆抗体的抑制，这表明这些细胞毒性效应细胞是CD3⁻CD8⁻，且来源于胸腺外。我们得出结论，在CD4⁺ T细胞恢复的裸鼠中，非胸腺来源的CD8⁺ GIC对同种异体移植排斥并非必不可少。
