Nishimura T, Nakamura Y, Takeuchi Y, Gao X H, Tokuda Y, Okumura K, Habu S
Department of Immunology, Tokai University School of Medicine, Isehara.
Jpn J Cancer Res. 1991 Nov;82(11):1207-10. doi: 10.1111/j.1349-7006.1991.tb01782.x.
Freshly isolated human CD4+ T cells can not respond to recombinant interleukin 2 (rIL-2) because of their lack of p75 IL-2 receptor expression. However, we succeeded in inducing a marked proliferation of purified CD4+ T cells by activation with rIL-2 plus anti-CD3 monoclonal antibody (mAb) cross-linked to a plastic plate. The proliferated CD4+ T cells produced a significant amount of IL-2 upon stimulation with phorbol ester plus A23187. Interestingly, CD4+ T cells activated with anti-CD3 mAb plus rIL-2 revealed a strong cytotoxic activity against Fc receptor (FcR)-positive tumor cells in the presence of anti-CD3 mAb. Moreover, the CD4+ T cells could lyse FcR-negative glioma cells by targeting with bispecific mAb containing anti-CD3 mAb and anti-glioma mAb. Thus, we demonstrated that rIL-2 and immobilized anti-CD3 mAb allowed the rapid generation of human CD4+ helper/killer T cells, which may be useful for the development of a new adoptive tumor immunotherapy.
新鲜分离的人CD4+ T细胞由于缺乏p75白细胞介素2(IL-2)受体表达,无法对重组白细胞介素2(rIL-2)作出反应。然而,我们通过用rIL-2加交联到塑料板上的抗CD3单克隆抗体(mAb)激活,成功诱导了纯化的CD4+ T细胞显著增殖。增殖的CD4+ T细胞在用佛波酯加A23187刺激后产生了大量的IL-2。有趣的是,在用抗CD3 mAb加rIL-2激活的CD4+ T细胞在抗CD3 mAb存在的情况下,对Fc受体(FcR)阳性肿瘤细胞显示出强大的细胞毒性活性。此外,CD4+ T细胞可以通过用含有抗CD3 mAb和抗胶质瘤mAb的双特异性mAb靶向裂解FcR阴性胶质瘤细胞。因此,我们证明rIL-2和固定化抗CD3 mAb能够快速产生人CD4+辅助/杀伤性T细胞,这可能对开发新的过继性肿瘤免疫疗法有用。