Interleukin-2 blocks the antitumour activity caused by depletion of CD25+ cells in a murine renal adenocarcinoma model
Article first published online: 24 JUN 2004
Volume 94, Issue 1, pages 171–176, July 2004
How to Cite
Takeuchi, T., Konno-Takahashi, N., Kasuya, Y., Ogushi, T., Nishimatsu, H. and Kitamura, T. (2004), Interleukin-2 blocks the antitumour activity caused by depletion of CD25+ cells in a murine renal adenocarcinoma model. BJU International, 94: 171–176. doi: 10.1111/j.1464-4096.2004.04876.x
- Issue published online: 24 JUN 2004
- Article first published online: 24 JUN 2004
- Accepted for publication 23 March 2004
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 α)-positive T cells elicits potent immune responses to syngeneic tumours in vivo.
MATERIALS AND METHODS
Aliquots of 1 × 104 or 1 × 105 RENCA cells were implanted into the subcapsule of the left kidney of syngeneic male Balb/c mice. Mice were injected with 125 µg of antimouse CD25 mAb to deplete CD25+ cells before RENCA implantation. Then 104 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.