van den Brink M R, Hunt L E, Hiserodt J C
Department of Pathology, University of Pittsburgh, Pennsylvania 15213.
J Exp Med. 1990 Jan 1;171(1):197-210. doi: 10.1084/jem.171.1.197.
We recently described a mAb 3.2.3 (IgG1), that recognizes a 60-kD dimeric molecule expressed exclusively on fresh and rIL-2-activated NK cells and polymorphonuclear cells. mAb 3.2.3 enhances cytolytic activity of NK cells against selected FcR+ tumor target cells by reverse antibody-dependent cellular cytotoxicity (ADCC), indicating that it recognizes an important triggering site on NK cells. The in vivo treatment of F344 rats with mAb 3.2.3 intraperitoneally completely and selectively eliminated NK/ADCC function in the spleen and peripheral blood for up to 10 d after treatment. Total numbers and percentages of T cells, monocytes, or PMN were not decreased and T cell function, as determined by Con A stimulation, was not affected. The reduction in NK function was associated with a decrease in the numbers of LGL and the expression of other NK-related cell surface markers including CD2, CD8, and asialo GM1. Depletion of NK cells with 3.2.3 markedly decreased the survival of F344 rats injected intravenously with MADB106 mammary adenocarcinoma cells, but did not affect the subcutaneous growth of MADB106 tumors. These results indicate that mAb 3.2.3 (in contrast to anti-asialo GM1 and OX8, which are less selective markers) will be useful for studies on the functional role of NK cells in vivo as well as their in vivo differentiation and origin from 3.2.3- precursors.
我们最近描述了一种单克隆抗体3.2.3（IgG1），它识别一种仅在新鲜的和经重组白细胞介素-2激活的自然杀伤（NK）细胞及多形核细胞上表达的60-kD二聚体分子。单克隆抗体3.2.3通过反向抗体依赖性细胞毒性（ADCC）增强NK细胞对选定的FcR+肿瘤靶细胞的细胞溶解活性，这表明它识别NK细胞上一个重要的触发位点。用单克隆抗体3.2.3对F344大鼠进行腹腔内体内治疗，在治疗后长达10天内完全且选择性地消除了脾脏和外周血中的NK/ADCC功能。T细胞、单核细胞或多形核细胞的总数和百分比没有降低，并且通过刀豆蛋白A刺激测定的T细胞功能也未受影响。NK功能的降低与大颗粒淋巴细胞（LGL）数量的减少以及包括CD2、CD8和脱唾液酸GM1在内的其他NK相关细胞表面标志物的表达降低有关。用3.2.3清除NK细胞显著降低了静脉注射MADB106乳腺腺癌细胞的F344大鼠的存活率，但不影响MADB106肿瘤的皮下生长。这些结果表明，单克隆抗体3.2.3（与选择性较差的标志物抗脱唾液酸GM1和OX8相比）将有助于研究NK细胞在体内的功能作用以及它们从3.2.3前体的体内分化和起源。
