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

Authors: Heier, I.; Hofgaard, P. O.; Brandtzæg, P.; Jahnsen, F. L.; Karlsson, M.

Source: Clinical & Experimental Immunology, Volume 152, Number 2, May 2008 , pp. 381-387(7)

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Abstract:

Summary

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.

Keywords: anti-tumour immunity; GITR; lymphoma; regulatory T cells

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2249.2008.03642.x

Publication date: 2008-05-01