The roles of antigen-specificity, responsiveness to transforming growth factor-β and antigen-presenting cell subsets in tumour-induced expansion of regulatory T cells.
In this study we investigated the impact of several factors on the expansion of natural regulatory T (nTreg) cells by tumours, including antigen specificity, transforming growth factor-β (TGF-β) signalling and the antigen-presenting cell subsets responsible for expansion. We found that antigen non-specific expansion of nTreg cells is tumour cell line-dependent. Although both antigen-specific and non-specific pathways can contribute to expansion, the migration of activated nTreg cells to tumour tissues is strictly antigen-dependent. Intact TGF-β signalling on nTreg cells is also essential for tumour-induced expansion. Finally, for stimulation of resting antigen-specific CD4 T cells, CD11c(+) cells purified from tumour-draining lymph nodes were more potent than CD11b(+) cells, suggesting that dendritic cells are the key antigen-presenting cell subset involved in cross-presentation of tumour antigens. This study not only provides an in vivo system in which cross-talk between nTreg cells and tumours can be explored but also reveals novel aspects of tumour immune evasion.
Coe
David
D
Cancer Immunotherapy Group, Section of Immunobiology, Department of Medicine, Imperial College London, London , UK.
Addey
Caroline
C
White
Matthew
M
Simpson
Elizabeth
E
Dyson
Julian
J
Chai
Jian-Guo
JG
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000473:pathology; D000951:Antigens, Neoplasm / Q000276:immunology*; D039521:CD11c Antigen / Q000276:immunology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D045142:Cross-Priming / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000276:immunology*; D019139:Tumor Escape / Q000276:immunology*
D000951:Antigens, Neoplasm; D039521:CD11c Antigen; D016212:Transforming Growth Factor beta