Sandberg J O, Korsgren O
Department of Clinical Immunology and Transfusion Medicine, Uppsala University, Sweden.
Transplantation. 1997 Aug 27;64(4):584-9. doi: 10.1097/00007890-199708270-00006.
Recently, inhibition of transplant rejection by pretreatment of xenogeneic pancreatic islets cells with antibodies to intercellular adhesion molecule (ICAM)-1 was reported. These promising results together with the development of mice deficient in P selectin or ICAM-1 encouraged further evaluation of the role of these two molecules in allo- and xenogeneic pancreatic islet transplantation. These deficient mice provide powerful tools to study the complex role of cell adhesion molecules in the cellular interactions between graft and recipient that culminate in graft rejection.
ICAM-1-deficient mice served as both donors and recipients, but P selectin-deficient mice served only as recipients, in allogeneic and concordant xenogeneic (mouse-to-rat) transplantations. Both ICAM-1- and P selectin-deficient mice served as recipients in discordant xenogeneic (pig to mouse) transplantations. Two hundred collagenase-isolated pancreatic islets or fetal porcine islet-like cell clusters were transplanted under the renal capsule of the recipients. Animals were killed 7 days after transplantation, and the rejection process was evaluated with immunohistochemical techniques.
The use of ICAM-1- or P selectin-deficient mice did not influence the infiltration of T cells, macrophages, or natural killer cells in the islet grafts. Nor did preincubation of islet-like cell clusters with ICAM-1 monoclonal antibody inhibit the xenogeneic rejection process. In allograft rejection, an equivalent number of T cells and macrophages were present. Among the T cells, the CD8-positive subtype dominated. Quite in contrast, macrophages were the dominating infiltrating cell type in the discordant xenografts. The pattern of cellular infiltration in the concordant xenografts was more complex and seemed to share components from both allo- and xenograft rejection.
Thus, disturbance of the expression of ICAM-1 or P selectin in either the recipient or in the islet-graft did not influence allo- or xenograft rejection.
最近，有报道称用抗细胞间黏附分子（ICAM）-1抗体预处理异种胰岛细胞可抑制移植排斥反应。这些有前景的结果，连同P选择素或ICAM-1基因缺陷小鼠的培育，促使人们进一步评估这两种分子在同种异体和异种胰岛移植中的作用。这些基因缺陷小鼠为研究细胞黏附分子在移植物与受体间细胞相互作用中的复杂作用提供了有力工具，这种相互作用最终导致移植物排斥。
在同种异体和协调性异种（小鼠到大鼠）移植中，ICAM-1基因缺陷小鼠同时作为供体和受体，但P选择素基因缺陷小鼠仅作为受体。在非协调性异种（猪到小鼠）移植中，ICAM-1和P选择素基因缺陷小鼠均作为受体。将200个用胶原酶分离的胰岛或胎猪胰岛样细胞团移植到受体的肾被膜下。移植7天后处死动物，并用免疫组化技术评估排斥过程。
使用ICAM-1或P选择素基因缺陷小鼠并不影响胰岛移植物中T细胞、巨噬细胞或自然杀伤细胞的浸润。用ICAM-1单克隆抗体预孵育胰岛样细胞团也不能抑制异种排斥过程。在同种异体移植排斥中，存在等量的T细胞和巨噬细胞。在T细胞中，CD8阳性亚型占主导。相比之下，巨噬细胞是非协调性异种移植物中占主导的浸润细胞类型。协调性异种移植物中的细胞浸润模式更为复杂，似乎兼具同种异体和异种移植排斥的成分。
因此，受体或胰岛移植物中ICAM-1或P选择素表达的紊乱并不影响同种异体或异种移植排斥。
