Kawamura T, Kawachi Y, Moroda T, Weerasinghe A, Iiai T, Seki S, Tazawa Y, Takada G, Abo T
Department of Pediatrics, Akita University School of Medicine, Japan.
Immunology. 1996 Sep;89(1):68-75. doi: 10.1046/j.1365-2567.1996.d01-719.x.
Morphological and phenotypic characterization in previous studies has indicated that intermediate (int) T-cell receptor (TCR) cells or T natural killer (TNK) cells may stand at an intermediate position between NK cells and high TCR cells of thymic origin in phylogenetic development. In this study, a functional study on cytotoxic activity against various tumour targets was performed in each purified subset. When a negative selection method entailing in vivo injection of anti-asialo GM, antibody or anti-interleukin (IL)-2R beta monoclonal antibody (mAb) was applied, IL-2R beta 1 CD3 NK cells were found to have the highest NK activity while IL-2R beta 1 int CD3 (or TCR) cells had a lower level of the NK activity. High CD3 cells (freshly isolated) did not have any such activity. Sorting experiments further revealed that the NK function mediated by int CD3 cells was augmented when they were exposed to anti-CD3 mAb. anti-TCR alpha beta, or anti-TCR-delta mAb. This phenomenon was not observed in NK cells and high CD3 cells. More importantly, when anti-CD3 mAb (or anti-TCR mAb) was added to the assay culture, int CD3 cells became cytotoxic against even NK-resistant tumour (Fc gamma R-. Fas+) targets. Liver mononuclear cells or int CD3 cells exposed to anti-CD3 mAb for 6 hr showed an elevated level of perforin in their cytoplasms. The present results suggest that int CD3 cells are usually non-cytotoxic against various tumours but become functional after being stimulated via the TCR CD3 complex.
先前研究中的形态学和表型特征表明,中间型(int)T细胞受体(TCR)细胞或T自然杀伤(TNK)细胞在系统发育过程中可能处于NK细胞和胸腺来源的高TCR细胞之间的中间位置。在本研究中,对每个纯化亚群针对各种肿瘤靶标的细胞毒性活性进行了功能研究。当采用体内注射抗去唾液酸GM抗体或抗白细胞介素(IL)-2Rβ单克隆抗体(mAb)的阴性选择方法时,发现IL-2Rβ1 CD3 NK细胞具有最高的NK活性,而IL-2Rβ1 int CD3(或TCR)细胞的NK活性水平较低。高CD3细胞(新鲜分离)没有任何此类活性。分选实验进一步表明,int CD3细胞在暴露于抗CD3 mAb、抗TCRαβ或抗TCRδ mAb时,其介导的NK功能增强。在NK细胞和高CD3细胞中未观察到这种现象。更重要的是,当将抗CD3 mAb(或抗TCR mAb)添加到检测培养物中时,int CD3细胞甚至对NK抗性肿瘤(FcγR-、Fas+)靶标具有细胞毒性。暴露于抗CD3 mAb 6小时的肝单核细胞或int CD3细胞在其细胞质中显示穿孔素水平升高。目前的结果表明,int CD3细胞通常对各种肿瘤无细胞毒性,但在通过TCR-CD3复合物刺激后变得具有功能。