Depletion of CD4+ CD25+ regulatory T cells inhibits local tumour growth in a mouse model of B cell lymphoma

Regulatory T cells (T-regs) may inhibit immunity against cancer. Induction and expansion of T-regs in the immunosuppressive microenvironment created by a growing tumour appear to be one of the mechanisms by which it can evade host defence. We studied the impact of CD25(+) T-regs in a B cell lymphoma model in which Rag2(-/-) mice received adoptive transfer of wild-type spleen cells with or without CD25(+) cells, and concurrently subcutaneous inoculation of the B cell lymphoma cell line A20. We also examined the effect of engaging the glucocorticoid-induced tumour necrosis factor receptor (GITR) - an approach reported previously to abrogate the suppressive effects of T-regs. Mice that received spleen cells depleted of CD25(+) T-regs showed significantly slower tumour growth and increased survival compared with mice that received unsorted spleen cells. The T-reg-depleted group also had significantly more CD8(+) T cells infiltrating the tumours and higher levels of serum immunoglobulin G subclasses. The anti-GITR treatment had no significant effect on tumour growth, survival or immunoglobulin production. In the CD25-depleted group four of 10 mice developed clinical signs of autoimmunity, in contrast to none in the non-depleted group. Forkhead box P3(+) T cells were found in tumour-draining lymph nodes in mice in the CD25-depleted group, suggesting an in vivo induction or expansion of rare transferred donor T-regs. Thus, our study showed that removal of CD25(+) T-regs enhanced anti-tumour immunity against local growth of a B cell lymphoma and that induction or expansion of T-regs could be one mechanism by which the growing tumour evades immune surveillance.