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题目:: CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-beta-dependent manner.
作者:: Ghiringhelli(François),Ménard(Cédric),Terme(Magali),Flament(Caroline),Taieb(Julien),Chaput(Nathalie),Puig(Pierre E),Novault(Sophie),Escudier(Bernard),Vivier(Eric),Lecesne(Axel),Robert(Caroline),Blay(Jean-Yves),Bernard(Jacky),Caillat-Zucman(Sophie),Freitas(Antonio),Tursz(Thomas),Wagner-Ballon(Orianne),Capron(Claude),Vainchencker(William),Martin(François),Zitvogel(Laurence)
状态:: 发布时间2005-10-18 , 更新时间 2014-09-10
期刊:: J Exp Med
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.
语言:: eng
DOI:

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