18 1 2006 2 Chinese Bulletin of Life Sciences Vol. 18, No1 Feb., 2006 1004-0374(2006)01-0062-05 NKT 1 200051 2 200062 NKT NK T NK NKT NKT R392.12; R730.3 A Functional role of natural killer T cells and their mechanisms in anti-tumor immunity YANG Jie 1,2, FAN Hua-Hua 1 *, ZHANG Ping 2, GAO Feng 1 (1 Shanghai (Red cross) Blood Center,Laboratory for Blood Engineering, Shanghai 200051, China; 2 Laboratory of Immunology, School of Life Sciences, East China Normal University, Shanghai 200062, China) Abstract: Natural killer T (NKT) cells are a population of T cells that share some characteristics with natural killer (NK) cells. After activated, NKT cells can kill tumors directly as the anti-tumor effectors and they can also activate other cell types, such as NK cells, to mediate anti-tumor effects indirectly. NKT cells play an important role in anti-tumor immunity, adaptive immune responses and immunoregulation. Key Words: NKT cells; anti-tumor function; anti-tumor mechanism T (natural killer T cells NKT ) T T B NK NKT T CD3 TCRαβ( Vα14Vβ8 Vα24Vβ11), NK NK1.1 CD16 CD122 NKT CD1d (MHC) α - ( α - galactosylceramide, α-galcer ) CD1d TCR NKT [1] NKT IL-4 IL-10 IL-13 IFN-γ NKT TNF-α NKT NKT [2] NKT 2005-07-22 2005-08-18 012B14057, 002B14053 1980 1966 * 1964 1943
NKT 63 1 NKT NKT TCR NKT 1.1 NKT IL-12 IL-12 NK T B16 IL-12, NKT NK [3] NKT IL-12 IL-12 NKT IL-12 NKT IL-12 NK IL-12 NKT IL-12 NKT IFN-γ NKT IL-12 [4] (DC) NKT IL-12 IL-12 NKT IL-12 NKT IL-18 IL-12 NKT IL-12 NKT [5] NKT IL-12 T [6] 1.2 α-galcer α-galcer CD1d α-galcer NKT β-galcer α-galcer NKT α-galcer NKT α-galcer [7] IL-21 [8] NKT NKT α-galcer NKT IL-12 NKT [2] : (1)NKT TCR CD1d α-galcer CD40/CD40 NKT IL-4 IFN-γ NKT IL-12R CD40L (2) IL-12 (3) IL-12 NKT IFN-γ NK CD8 + T 2 NKT NKT Jα281TCR [9] NKT 2.1 NKT Kawano [10] Vα24 NKT α-galcer HMV-1( ) PANC-1( ) HeLa( ) Vα24 NKT Takahashi [11] Metelitsa [12] Vα24 NKT Gansuvd [13] NKT (4 h) NKT CD1d (20 h) NKT CD1d NKT NKT NKT MHC α-galcer/cd1d-nkt NKT 2.2 NKT Ishikawa [14] Konishi [15] α-galcer DC Vα24 NKT Fas/FasL α-galcer NKT IFN-γ, [16] Chang [17] α-galcer NKT IL-12 IFN-γ CD8 + T NKT T NK
64 CD1d [3] 3 NKT NKT NKT NK NKT 3.1 NKT NKT Fas/FasL TNF-α NKT FasL Fas NKT TNF-α NK Cui [3] Kawano [18] anti-fas/fasl anti-nk1. 1 anti-vβ8 anti- IFN-γ anti-cdld NKT A(CMA) Gansuvd [13] CD1d CD1d NKT Fas TNF-α TNF-α IL-4 IL-12 α-galcer CD1d TCR CD1d [19] NKT (tumor necrosis factor-related apoptosisinducing ligand TRAIL) [12] 3.2 NKT IFN-γ NK DC CD4Th1 CD8 + T [20~21] NKT [2] : (1) IL-12 IL-12 NKT NK IL-12 NKT NKT NK IFN-γ NK IL-12 NKT IL-12 (2) α-galcer α-galcer CD1d CD1d NKT IL-12 CD8 + (3) NKT IL-12 IFN CD8 + NKT NK CD8 + T B NK1.1 NK [22] NK NKT IL-2 [23] IL-12 NK NKT T B NKT NK NK [20] 4 NKT NKT NKT α-galcer IL-12 NKT Moodycliffe [24] NKT T NKT Terabe [25] NKT
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66 nonspecific tumor cell lysis mediated by specific ligandactivated Vα 14 NKT cells. Proc Natl Acad Sci USA, 1998, 95(10): 5690~5693 [19] Nicol A, Nieda M, Koezuka Y, et al. Human invariant Vα 24 + natural killer T cells activated by α-galactosylceramide (KRN7000) have cytotoxic anti-tumour activity through mechanisms distinct from T cells and natural killer cells. Immunology, 2000, 99(2): 229~234 [20] Hayakawa Y, Takeda K, Yagita H, et al. Critical contribution of IFN-α and NK cells, but not perforin-mediated cytotoxicity, to anti-metastatic effect of α- galactosylceramide. Eur J Immunol, 2001, 31(6): 1720~1727 [21] Kitamura H, Iwakabe K, Yahata T, et al. The natural killer T (NKT) cell ligand α-galactosylceramide demonstrates its immunopotentiating effect by inducing interleukin (IL)-12 production by dendritic cells and IL-12 receptor expression on NKT cells. J Exp Med, 1999, 189(7): 1121~1128 [22] Carnaud C, Lee D, Donnars O, et al. Cutting edge: cross-talk between cells of the innate immune system: NKT cells rapidly activate NK cells. J Immunol, 1999, 163(9): 4647~4650 [23] Metelitsa L S, Naidenko O V, Kant A, et al. Human NKT cells mediate antitumor cytotoxicity directly by recognizing target cell CD1d with bound ligand or indirectly by producing IL-2 to activate NK cells. J Immunol, 2001, 167(6): 3114~3122 [24] Moodycliffe A M, Nghiem D, Clydesdale G, et al. Immune suppression and skin cancer development: regulation by NKT cells. Nat Immunol, 2000, 1(6): 521~525 [25] Terabe M, Matsui S, Noben-Trauth N, et al. NKT cellmediated repression of tumor immunosurveillance by IL-13 and the IL-4R-STAT6 pathway. Nat Immunol, 2000, 1(6): 515~520 [26] Gumperz J E. CD1d-restricted NKT cells and myeloid IL- 12 production: an immunological crossroads leading to promotion or suppression of effective anti-tumor immune responses? J Leukoc Biol, 2004, 76(2): 307~313 2005 10 26 (Medical Research Council Technology) 50 15 93 23 http: //www.sibs.ac.cn