The impact of regulatory T cells on carcinogen-induced sarcogenesis.
Burnet proposed in the 1950's that the immune system is engaged in identifying and destroying abnormal cancerous cells. This process, termed immune surveillance, has been at the centre of intense debate for decades. Results using immunodeficient mice lend support to the immune surveillance hypothesis. We surmised that immune surveillance would be hampered by the inhibitory effect of naturally occurring FoxP3(+) regulatory T cells, a population of T cells shown to be present at an increased frequency in a variety of human tumours. The carcinogen, methylcholanthrene was injected subcutaneously into mice and the steady development of fibrosarcomas was observed over approximately 200 days. These fibrosarcomas were strikingly infiltrated with FoxP3(+) regulatory T cells implying that these cells impinge upon immune-mediated rejection of the tumour. This was confirmed by partial ablation of FoxP3(+) regulatory T-cell activity, which resulted in a marked reduction in tumour incidence. The reduction of tumour incidence was ablated in mice that lacked interferon gamma. These data offer strong support for the concept of immune surveillance and indicate that this process is limited by the inhibitory effect of FoxP3(+) regulatory T cells.
Betts
G
G
Medical Biochemistry and Immunology, Henry Wellcome Building, Heath Park, Cardiff, CF14 4XN, UK. bettsgj@cf.ac.uk
Twohig
J
J
Van den Broek
M
M
Sierro
S
S
Godkin
A
A
Gallimore
A
A
D000818:Animals; D001323:Autoantibodies / Q000032:analysis; D002273:Carcinogens; D005260:Female; D005354:Fibrosarcoma / Q000139:chemically induced / Q000276:immunology*; D007371:Interferon-gamma / Q000172:deficiency; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008212:Lymphocyte Depletion; D008748:Methylcholanthrene; D051379:Mice; D018345:Mice, Knockout; D012513:Sarcoma, Experimental / Q000139:chemically induced / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D001323:Autoantibodies; D002273:Carcinogens; D053645:Interleukin-2 Receptor alpha Subunit; D008748:Methylcholanthrene; D007371:Interferon-gamma