BACKGROUND & AIMS:
WT 1, an IgG2a subclass monoclonal antibody, recognizes a human T lineage specific antigen (mol. wt 40,000). This antigen is strongly expressed on thymic T blasts, and on peripheral T cells activated by phytohaemagglutinin, whereas cortical thymocytes and peripheral T cells are moderately positive for WT 1. In contrast, B lymphocytes, myeloid and erythroid cells, including the progenitor cells of these lineages, and terminal deoxynucleotidyl transferase positive cells in the bone marrow, are all WT 1 negative. Binding of WT 1 to T cells is blocked by a previously described antibody (3A1) suggesting that both antibodies bind to the same antigen present on human T cells. WT 1, however, is also reactive with T lymphocytes from rhesus monkeys whereas 3A1 is not. Therefore, the biological effects of WT 1 could be studied in a monkey model. In a skin allograft model, WT 1 was immunosuppressive and induced a marked prolongation of graft survival.
背景与目标:
IgG2a亚类单克隆抗体WT 1识别人T谱系特异性抗原 (mol. wt 40,000)。该抗原在胸腺T细胞和被植物血凝素激活的外周T细胞上强烈表达,而皮质胸腺细胞和外周T细胞对WT 1呈中等阳性。相反,B淋巴细胞,髓样和红系细胞 (包括这些谱系的祖细胞) 以及骨髓中的末端脱氧核苷酸转移酶阳性细胞均为WT 1阴性。WT 1与T细胞的结合被先前描述的抗体 (3A1) 阻断,这表明两种抗体与存在于人T细胞上的相同抗原结合。但是,WT 1也与恒河猴的T淋巴细胞反应,而3A1则没有。因此,可以在猴子模型中研究WT 1的生物学效应。在同种异体皮肤移植模型中,WT 1具有免疫抑制作用,并显着延长了移植物的存活时间。