Takeuchi Takumi, Konno-Takahashi Naoko, Kasuya Yutaka, Ogushi Tetsuo, Nishimatsu Hiroaki, Kitamura Tadaichi
Department of Urology, Faculty of Medicine, University of Tokyo, Japan.
BJU Int. 2004 Jul;94(1):171-6. doi: 10.1111/j.1464-4096.2004.04876.x.
To test the effectiveness of antimouse CD25 monoclonal antibody (mAb) against murine renal adenocarcinoma (RENCA) cells, as immunoregulatory/suppressor cells are known to be involved in tumour development in vivo, but the functions of these cells are not yet clear, and eliminating naive CD25 (interleukin-2 receptor alpha)-positive T cells elicits potent immune responses to syngeneic tumours in vivo.
Aliquots of 1 x 10(4) or 1 x 10(5) RENCA cells were implanted into the subcapsule of the left kidney of syngeneic male Balb/c mice. Mice were injected with 125 micro g of antimouse CD25 mAb to deplete CD25(+) cells before RENCA implantation. Then 10(4) units of recombinant human interleukin-2 (rhIL-2) were subcutaneously injected twice daily for 7 days. Fourteen or 25 days later the tumour size was determined by laparotomy, and cells sorted using two-colour flow cytometry.
Depletion of naive CD25(+) cells with anti-CD25 mAb and rhIL-2 administration effectively induced anti-RENCA tumour activity in Balb/c hosts. However, co-administration of anti-CD25 mAb and rhIL-2 abrogated this significant suppression of RENCA tumour growth. RENCA implantation reduced the proportion of CD4(+) cells among splenocytes, whereas anti-CD25 mAb treatment increased it. The proportion of CD25(+)CD8(+) cells among splenocytes and that of CD25(+) cells among CD8(+) cells were markedly reduced by co-administration of anti-CD25 mAb and rhIL-2 with RENCA implantation. Both CD4(+) and CD8(+) cells were stained around the remnant microscopic RENCA tumour after anti-CD25 mAb treatment.
Either depletion of naive CD25(+) cells or rhIL-2 administration suppressed RENCA tumour growth in murine hosts. However, co-administration of anti-CD25 mAb and rhIL-2 abrogated this significant suppression of RENCA tumour growth.
已知免疫调节/抑制细胞参与体内肿瘤的发展，但其功能尚不清楚，且清除初始CD25（白细胞介素-2受体α）阳性T细胞可在体内引发对同基因肿瘤的有效免疫反应，本研究旨在测试抗小鼠CD25单克隆抗体（mAb）对小鼠肾腺癌（RENCA）细胞的有效性。
将1×10⁴或1×10⁵个RENCA细胞的等分试样植入同基因雄性Balb/c小鼠左肾被膜下。在植入RENCA细胞前，给小鼠注射125μg抗小鼠CD25 mAb以清除CD25⁺细胞。然后每天皮下注射10⁴单位重组人白细胞介素-2（rhIL-2），共7天。14或25天后，通过剖腹术确定肿瘤大小，并使用双色流式细胞术对细胞进行分选。
用抗CD25 mAb清除初始CD25⁺细胞并给予rhIL-2可有效诱导Balb/c宿主产生抗RENCA肿瘤活性。然而，抗CD25 mAb和rhIL-2联合给药消除了对RENCA肿瘤生长的显著抑制作用。植入RENCA细胞降低了脾细胞中CD4⁺细胞的比例，而抗CD25 mAb治疗则使其增加。抗CD25 mAb和rhIL-2与RENCA细胞联合植入可显著降低脾细胞中CD25⁺CD8⁺细胞的比例以及CD8⁺细胞中CD25⁺细胞的比例。抗CD25 mAb治疗后，在残留的微小RENCA肿瘤周围，CD4⁺和CD8⁺细胞均被染色。
清除初始CD25⁺细胞或给予rhIL-2均可抑制小鼠宿主中RENCA肿瘤的生长。然而，抗CD25 mAb和rhIL-2联合给药消除了对RENCA肿瘤生长的显著抑制作用。
