CD4+ CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-β-dependent manner

被引:730
作者
Ghiringhelli, F
Ménard, C
Terme, M
Flament, C
Taieb, J
Chaput, N
Puig, PE
Novault, S
Escudier, B
Vivier, E
Lecesne, A
Robert, C
Blay, JY
Bernard, J
Caillat-Zucman, S
Freitas, A
Tursz, T
Wagner-Ballon, O
Capron, C
Vainchencker, W
Martin, F
Zitvogel, L [1 ]
机构
[1] Univ Paris 11, INSERM, ERM 0208, Orsay, France
[2] Inst Gustave Roussy, Unite Immunotherapie, F-94805 Villejuif, France
[3] Inst Gustave Roussy, Dept Med Oncol, F-94805 Villejuif, France
[4] Inst Gustave Roussy, INSERM, U362, F-94805 Villejuif, France
[5] Univ Burgundy, Fac Med, INSERM, U517, F-21079 Dijon, France
[6] CNRS, INSERM, Ctr Immunol, F-13288 Marseille, France
[7] Hop Edouard Herriot, Hospices Civils Lyon, F-69003 Lyon, France
[8] Etablissement Francais Sang, Ctr Jean Godineau, F-51056 Reims, France
[9] Assistance Publ Hop Paris, Hop St Vincent de Paul, INSERM, U561, F-75674 Paris, France
[10] CNRS, Unite Biol Populat Lymphocytaires, F-75015 Paris, France
关键词
D O I
10.1084/jem.20051511
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Tumor growth promotes the expansion of CD4(+) CD25(+) regulatory T (T reg) cells that counteract T cell-mediated immune responses. An inverse correlation between natural killer (NK) cell activation and T reg cell expansion in tumor-bearing patients, shown here, prompted us to address the role of T reg cells in controlling innate antitumor immunity. Our experiments indicate that human T reg cells expressed membrane-bound transforming growth factor (TGF)-beta, which directly inhibited NK cell effector functions and down-regulated NKG2D receptors on the NK cell surface. Adoptive transfer of wild-type T reg cells but not TGF-beta(-/-) T reg cells into nude mice suppressed NK cell-mediated cytotoxicity, reduced NKG2D receptor expression, and accelerated the growth of tumors that are normally controlled by NK cells. Conversely, the depletion of mouse T reg cells exacerbated NK cell proliferation and cytotoxicity in vivo. Human NK cell-mediated tumor recognition could also be restored by depletion of T reg cells from tumor-infiltrating lymphocytes. These findings support a role for T reg cells in blunting the NK cell arm of the innate immune system.
引用
收藏
页码:1075 / 1085
页数:11
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