1. CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-beta-dependent manner
- Author
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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), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
- 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 - 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.
- Published
- 2007
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