Depletion of CD25+ regulatory cells results in suppression of melanoma growth and induction of autoreactivity in mice.
Treatment with monoclonal antibodies (mAbs) specific for CD25 (anti-CD25 mAb) has been shown to suppress growth of a variety of different tumours in mice. These studies did not however determine whether or not anti-CD25 mAbs facilitate tumour rejection by depletion of regulatory T cells or by binding to tumour-specific effector cells. Using a murine model of melanoma we have found that treatment of mice with anti-CD25 mAb facilitates long-term CD4+ T cell-mediated tumour immunity through depletion of CD25+ regulatory cells. We further show that the effector CD4+ T cells confer long-term tumour immunity even in the presence of CD25+ regulatory cells and do not require CD8+ T cells for tumour rejection. The inhibitory impact of anti-CD25 mAb treatment on tumour growth may be the result of depleting CD25+ regulatory cells that normally inhibit the generation of immune responses to self-antigens that are shared by the tumour. We have performed experiments to determine whether or not immune responses to melanocyte antigens are generated in anti-CD25 mAb-treated, melanoma-immune mice. The results of the experiments indicate that a T cell response to the melanocyte antigen tyrosinase accompanies suppression of tumour growth in mice lacking CD25+ regulatory cells.
Nuffield Department of Medicine, Molecular Immunology Group, John Radcliffe Hospital, Oxford.
Emma
E
Jones
Michaela
M
Dahm-Vicker
Anna Katharina
AK
Simon
Angharad
A
Green
Fiona
F
Powrie
Vincenzo
V
Cerundolo
Awen
A
Gallimore
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000943:Antigens, Differentiation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors; D007167:Immunotherapy; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D014442:Monophenol Monooxygenase / Q000627:therapeutic use; D009368:Neoplasm Transplantation; D016609:Neoplasms, Second Primary / Q000517:prevention & control; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured; D014616:Vaccinia virus / Q000235:genetics
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D014442:Monophenol Monooxygenase