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

Clin Exp Immunol. 2008 May;152(2):381-7. doi: 10.1111/j.1365-2249.2008.03642.x. Epub 2008 Mar 12.


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.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibodies, Monoclonal / immunology
  • Cell Division
  • Disease Models, Animal
  • Glucocorticoid-Induced TNFR-Related Protein
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / blood
  • Immunophenotyping
  • Interleukin-2 Receptor alpha Subunit / analysis*
  • Lymphocyte Depletion*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphoma, B-Cell / immunology*
  • Lymphoma, B-Cell / pathology
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Transplantation
  • Receptors, Nerve Growth Factor / immunology
  • Receptors, Tumor Necrosis Factor / immunology
  • Spleen / immunology
  • T-Lymphocytes, Regulatory / immunology*


  • Antibodies, Monoclonal
  • Glucocorticoid-Induced TNFR-Related Protein
  • Immunoglobulin G
  • Interleukin-2 Receptor alpha Subunit
  • Receptors, Nerve Growth Factor
  • Receptors, Tumor Necrosis Factor
  • Tnfrsf18 protein, mouse