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

Authors :
Jacky Bernard
Antônio C. Freitas
Jean-Yves Blay
Caroline Flament
Orianne Wagner-Ballon
Laurence Zitvogel
Cédric Ménard
A. Lecesne
Magali Terme
T. Tursz
Caroline Robert
Bernard Escudier
William Vainchencker
Eric Vivier
Claude Capron
Julien Taieb
Sophie Caillat-Zucman
François Ghiringhelli
Sophie Novault
Nathalie Chaput
Pierre E. Puig
François Martin
Rôle des cellules dendritiques dans la régulation des effecteurs de l'immunité antitumorale
Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )
Mort cellulaire et cancer
Université de Bourgogne ( UB ) -IFR100 - Structure fédérative de recherche Santé-STIC-Institut National de la Santé et de la Recherche Médicale ( INSERM )
Hematopoïèse et Cellules Souches ( U362 )
Centre d'Immunologie de Marseille - Luminy ( CIML )
Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )
Centre Jean Godineau
Etablissement Français du Sang
Immunologie, génétique et traitement des maladies métaboliques et du diabète ( UMR_S 561 )
Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 )
Biologie des Populations Lymphocytaires
Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS )
Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC-Institut National de la Santé et de la Recherche Médicale (INSERM)
Hematopoïèse et Cellules Souches (U362)
Centre d'Immunologie de Marseille - Luminy (CIML)
Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Immunologie, génétique et traitement des maladies métaboliques et du diabète (UMR_S 561)
Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]
Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)
Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Source :
The Journal of Experimental Medecine, The Journal of Experimental Medecine, The Rockefeller University Press, 2007, 202 (8), pp.1075-85. 〈10.1084/jem.20051511〉, Journal of Experimental Medicine, Journal of Experimental Medicine, Rockefeller University Press, 2007, 202 (8), pp.1075-85. ⟨10.1084/jem.20051511⟩, Journal of Experimental Medicine, 2007, 202 (8), pp.1075-85. ⟨10.1084/jem.20051511⟩, The Journal of Experimental Medicine, The Journal of Experimental Medecine, The Rockefeller University Press, 2007, 202 (8), pp.1075-85. ⟨10.1084/jem.20051511⟩
Publication Year :
2007
Publisher :
HAL CCSD, 2007.

Abstract

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)–β, 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-β−/− 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.

Subjects

Subjects :
MESH : Cytokines
MESH: Flow Cytometry
MESH : Immunity, Natural
MESH: T-Ly
Lymphocyte Activation
T-Lymphocytes, Regulatory
Mice
Interleukin 21
0302 clinical medicine
T-Lymphocyte Subsets
Transforming Growth Factor beta
Neoplasms
MESH : Receptors, Immunologic
MESH : Cell Proliferation
Immunology and Allergy
[ SDV.IMM ] Life Sciences [q-bio]/Immunology
MESH: Animals
MESH: Neoplasms
IL-2 receptor
Receptors, Immunologic
0303 health sciences
MESH: Cytokines
hemic and immune systems
Flow Cytometry
Natural killer T cell
3. Good health
Cell biology
Killer Cells, Natural
medicine.anatomical_structure
NK Cell Lectin-Like Receptor Subfamily K
Interleukin 12
Cytokines
Receptors, Natural Killer Cell
[SDV.IMM]Life Sciences [q-bio]/Immunology
France
MESH : Killer Cells, Natural
MESH : Cytotoxicity Tests, Immunologic
MESH: Killer Cells, Natural
MESH: Cell Line, Tumor
MESH : Flow Cytometry
Immunology
chemical and pharmacologic phenomena
MESH: Cytotoxicity Tests, Immunologic
MESH : Mice, Inbred C57BL
Biology
Article
Natural killer cell
03 medical and health sciences
MESH: Mice, Inbred C57BL
Cell Line, Tumor
MESH: Cell Proliferation
MESH : Mice
medicine
Animals
Humans
Antigen-presenting cell
MESH: Lymphocyte Activation
MESH : France
MESH: Mice
MESH: Receptors, Immunologic
MESH : Lymphocyte Activation
Cell Proliferation
030304 developmental biology
MESH: Immunity, Natural
Lymphokine-activated killer cell
MESH: Humans
MESH : Cell Line, Tumor
MESH : Humans
Cytotoxicity Tests, Immunologic
NKG2D
MESH : T-Ly
MESH : Neoplasms
Immunity, Innate
Mice, Inbred C57BL
MESH: France
MESH : Animals
030215 immunology

Details

Language :
English
ISSN :
00221007 and 15409538
Database :
OpenAIRE
Journal :
The Journal of Experimental Medecine, The Journal of Experimental Medecine, The Rockefeller University Press, 2007, 202 (8), pp.1075-85. 〈10.1084/jem.20051511〉, Journal of Experimental Medicine, Journal of Experimental Medicine, Rockefeller University Press, 2007, 202 (8), pp.1075-85. ⟨10.1084/jem.20051511⟩, Journal of Experimental Medicine, 2007, 202 (8), pp.1075-85. ⟨10.1084/jem.20051511⟩, The Journal of Experimental Medicine, The Journal of Experimental Medecine, The Rockefeller University Press, 2007, 202 (8), pp.1075-85. ⟨10.1084/jem.20051511⟩
Accession number :
edsair.doi.dedup.....b791bcbfbd2e6ea289bfc7c48d8dc8c6