Interleukin‐2 blocks the antitumour activity caused by depletion of CD25 + cells in a murine renal adenocarcinoma model

OBJECTIVE 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 × 10 4 or 1 × 10 5 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 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. RESULTS 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. CONCLUSION 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.