共 47 条
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
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机构: Univ Paris 11, INSERM, ERM 0208, Orsay, France

Ménard, C
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机构: Univ Paris 11, INSERM, ERM 0208, Orsay, France

Terme, M
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机构: Univ Paris 11, INSERM, ERM 0208, Orsay, France

Flament, C
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机构: Univ Paris 11, INSERM, ERM 0208, Orsay, France

Taieb, J
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机构: Univ Paris 11, INSERM, ERM 0208, Orsay, France

Chaput, N
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机构: Univ Paris 11, INSERM, ERM 0208, Orsay, France

Puig, PE
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Novault, S
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Escudier, B
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Vivier, E
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Lecesne, A
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机构: Univ Paris 11, INSERM, ERM 0208, Orsay, France

Robert, C
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机构: Univ Paris 11, INSERM, ERM 0208, Orsay, France

Blay, JY
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Bernard, J
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Caillat-Zucman, S
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Freitas, A
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Tursz, T
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Wagner-Ballon, O
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机构: Univ Paris 11, INSERM, ERM 0208, Orsay, France

Capron, C
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机构: Univ Paris 11, INSERM, ERM 0208, Orsay, France

Vainchencker, W
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机构: Univ Paris 11, INSERM, ERM 0208, Orsay, France

Martin, F
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机构: Univ Paris 11, INSERM, ERM 0208, Orsay, France

Zitvogel, L
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h-index: 0
机构:
Univ Paris 11, INSERM, ERM 0208, Orsay, France Univ Paris 11, INSERM, ERM 0208, Orsay, France
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.
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页码:1075 / 1085
页数:11
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机构: Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA

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机构: Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA

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机构: Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA

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机构: Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA

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机构: Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA

Evdemon-Hogan, M
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机构: Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA

Conejo-Garcia, JR
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h-index: 0
机构: Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA

Zhang, L
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机构: Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA

Burow, M
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h-index: 0
机构: Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA

Zhu, Y
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h-index: 0
机构: Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA

Wei, S
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h-index: 0
机构: Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA

Kryczek, I
论文数: 0 引用数: 0
h-index: 0
机构: Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA

Daniel, B
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h-index: 0
机构: Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA

Gordon, A
论文数: 0 引用数: 0
h-index: 0
机构: Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA

Myers, L
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h-index: 0
机构: Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA

Lackner, A
论文数: 0 引用数: 0
h-index: 0
机构: Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA

Disis, ML
论文数: 0 引用数: 0
h-index: 0
机构: Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA

Knutson, KL
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h-index: 0
机构: Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA

Chen, LP
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h-index: 0
机构: Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA

Zou, WP
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h-index: 0
机构:
Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA
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机构: Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA

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机构: Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA

Liu, SD
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机构: Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA

Shastri, N
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h-index: 0
机构: Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA

Raulet, DH
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h-index: 0
机构: Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA