Kusunoki Y, Chen W, Martin P J
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Blood. 1998 Jun 1;91(11):4038-44.
In allogeneic marrow transplantation, donor T cells that recognize recipient alloantigens prevent rejection but also cause graft-versus-host disease (GVHD). To evaluate whether the ability to prevent marrow graft rejection could be dissociated from the ability to cause GVHD, we generated a panel of four different CD8 cytotoxic T-lymphocyte clones specific for H2(d) alloantigens. Three of the clones caused no overt toxicity when as many as 20 x 10(6) cells were infused intravenously into irradiated H2(d)-positive recipients, and one clone caused acute lethal toxicity within 1 to 3 days after transferring 10 x 10(6) cells into H2(d)-positive recipients. One clone that did not cause toxicity was able to prevent rejection of (C57BL/6J x C3H/HeJ)F1 marrow in 800 cGy-irradiated (BALB/cJ x C57BL/6J)F1 recipients without causing GVHD. Large numbers of cells and exogenously administered interleukin-2 were required to prevent rejection. These results with different CD8 clones suggest that GVHD and prevention of rejection could be separable effects mediated by distinct populations of donor T cells that recognize recipient alloantigens.
在同种异体骨髓移植中，识别受体同种异体抗原的供体T细胞可防止排斥反应，但也会引发移植物抗宿主病（GVHD）。为了评估防止骨髓移植排斥反应的能力是否可以与引发GVHD的能力相分离，我们构建了一组针对H2(d)同种异体抗原的四种不同的CD8细胞毒性T淋巴细胞克隆。当将多达20×10⁶个细胞静脉注射到经照射的H2(d)阳性受体中时，其中三个克隆未引起明显毒性，而将10×10⁶个细胞转移到H2(d)阳性受体中后，有一个克隆在1至3天内导致急性致死毒性。有一个未引起毒性的克隆能够防止800 cGy照射的（BALB/cJ×C57BL/6J）F1受体排斥（C57BL/6J×C3H/HeJ）F1骨髓，且不引发GVHD。需要大量细胞和外源性给予白细胞介素-2来防止排斥反应。这些不同CD8克隆的结果表明，GVHD和防止排斥反应可能是由识别受体同种异体抗原的不同供体T细胞群体介导的可分离效应。
