Collins T, Krensky A M, Clayberger C, Fiers W, Gimbrone M A, Burakoff S J, Pober J S
J Immunol. 1984 Oct;133(4):1878-84.
Monoclonal antibodies (mAb) against cell surface structures have been used to identify several molecules involved in the interaction of human cytolytic T lymphocytes (CTL) with lymphoid and other bone marrow-derived targets. In allograft rejection or in graft-vs-host disease, however, major cellular targets are vascular and stromal cells, especially endothelium. Yet little is known about whether the same cell surface molecules are involved in the interactions of CTL with these cell types. We assessed the ability of mAb against effector or target cell structures to inhibit cytolysis of susceptible, cultured human vascular endothelium or dermal fibroblasts by a cloned human CTL line. Using mAb reactive with T3, T4, LFA-1, LFA-2, LFA-3, and HLA-DR, we found a qualitatively similar but quantitatively different pattern of inhibition of cytolysis as previously established for lymphoid targets by using the same CTL clone. These results have two implications: 1) the target cell structures recognized by CTL molecules such as T4, LFA-1 and LFA-2 are present on diverse cell types; and 2) the relative importance of such interactions may vary with target cell type. Furthermore, our studies provide several insights into the mechanisms of the interacting molecules. Our model system, and the use of pathophysiologically important target cells, may be useful for further analysis of CTL-mediated immune injury.
针对细胞表面结构的单克隆抗体(mAb)已被用于鉴定几种参与人细胞毒性T淋巴细胞(CTL)与淋巴细胞及其他骨髓来源靶细胞相互作用的分子。然而,在同种异体移植排斥反应或移植物抗宿主病中,主要的细胞靶标是血管和基质细胞,尤其是内皮细胞。然而,对于相同的细胞表面分子是否参与CTL与这些细胞类型的相互作用,人们知之甚少。我们评估了针对效应细胞或靶细胞结构的单克隆抗体抑制克隆的人CTL系对易感的培养人血管内皮细胞或真皮成纤维细胞进行细胞溶解的能力。使用与T3、T4、LFA-1、LFA-2、LFA-3和HLA-DR反应的单克隆抗体,我们发现细胞溶解抑制模式在质量上与之前使用相同CTL克隆针对淋巴细胞靶标所确定的模式相似,但在数量上有所不同。这些结果有两个含义:1)CTL分子(如T4、LFA-1和LFA-2)识别的靶细胞结构存在于多种细胞类型上;2)这种相互作用的相对重要性可能因靶细胞类型而异。此外,我们的研究为相互作用分子的机制提供了一些见解。我们的模型系统以及使用具有病理生理学重要性的靶细胞,可能有助于进一步分析CTL介导的免疫损伤。