Chinese Bulletin of Life Sciences. Functional role of natural killer T cells and their mechanisms in anti-tumor immunity

Μέγεθος: px

Εμφάνιση ξεκινά από τη σελίδα:

Download "Chinese Bulletin of Life Sciences. Functional role of natural killer T cells and their mechanisms in anti-tumor immunity"

Θεοδοσία Αξιώτης
5 χρόνια πριν
Προβολές:

1 Chinese Bulletin of Life Sciences Vol. 18, No1 Feb., (2006) NKT 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 , China; 2 Laboratory of Immunology, School of Life Sciences, East China Normal University, Shanghai , 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 B14057, 002B *

2 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

3 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

4 NKT 65 IL-13, IL-12 (transforming growth factor-β,tgf-β) IL-4R-STAT6 CTL NKT NKT, (IFN-γ) (IL-4 IL-13) NKT IL-12R NK1.1 NKT IFN-γ IL-7 IL-4 IL-13 IL-18 NKT [2] NKT NKT CD40L DC IL-12 T Th1 NKT DC IL-10 IL-12 T Th1 [26] NKT NKT 5 NKT IL-12 α- GalCer NKT MHC-I MHC NKT NKT [1] Godfrey D I, Hammond K J, Poulton L D, et al. NKT cells: facts, functions and fallacies. Immunol Today, 2000, 21(11): 573~583 [2] Smyth M J, Crowe N Y, Hayakawa Y, et al. NKT cells - conductors of tumor immunity? Curr Opin Immunol, 2002, 14(2): 165~171 [3] Cui J Q, Shin T, Kawano T, et al. Requirement for Vα14 NKT cells in IL-12-mediated rejection of tumors. Science, 1997, 278(5343): 1623~1626 [4] Takeda K, Hayakawa Y, Atsuta M, et al. Relative contribution of NK and NKT cells to the anti-metastatic activities of IL-12. Int Immunol, 2000, 12(6): 909~914 [5] Eberl G, MacDonald H R. Rapid death and regeneration of NKT cells in anti-cd3epsilon- or IL-12-treated mice: a major role for bone marrow in NKT cell homeostasis. Immunity, 1998, 9(3): 345~353 [6] Brutkiewicz R R, Sriram V. Natural killer T (NKT) cells and their role in antitumor immunity. Crit Rev Oncol Hematol, 2002, 41(3): 287~298 [7] Hong S, Scherer D C, Singh N, et al. Lipid antigen presentation in the immune system: lessons learned from CD1d knockout mice. Immunol Rev, 1999, 169: 31~44 [8] Smyth M J, Wallace M E, Nutt S L, et al. Sequential activation of NKT cells and NK cells provides effective innate immunotherapy of cancer. J Exp Med, 2005, 201(12): 1973~1985 [9] Smyth M J, Thia K Y, Street S E, et al. Differential tumor surveillance by natural killer (NK) and NKT cells. J Exp Med, 2000, 191(4): 661~668 [10] Kawano T, Nakayama T, Kamada N, et al. Antitumor cytotoxicity mediated by ligand-activated human Vα 24 NKT cells. Cancer Res, 1999, 59(20): 5102~5105 [11] Takahashi T, Haraguchi K, Chiba S, et al. Vα 24 + natural killer T-cell responses against T-acute lymphoblastic leukaemia cells: implications for immunotherapy. Br J Haematol, 2003, 122(2): 231~239 [12] Metelitsa L S, Weinberg K I, Emanuel P D, et al. Expression of CD1d by myelomonocytic leukemias provides a target for cytotoxic NKT cells. Leukemia, 2003, 17(6): 1068~1077 [13] Gansuvd B, Hagihara M, Yu Y, et al. Human umbilical cord blood NK T cells kill tumors by multiple cytotoxic mechanisms. Hum Immunol, 2002, 63(3): 164~175 [14] Ishikawa A, Motohashi S, Ishikawa E, et al. A phase I study of α-galactosylceramide (KRN7000)-pulsed dendritic cells in patients with advanced and recurrent non-small cell lung cancer. Clin Cancer Res, 2005, 11(5): 1910~1917 [15] Konishi J, Yamazaki K, Yokouchi H, et al. The characteristics of human NKT cells in lung cancer-cd1d independent cytotoxicity against lung cancer cells by NKT cells and decreased human NKT cell response in lung cancer patients. Hum Immunol, 2004, 65(11): 1377~1388 [16] Seki S, Habu Y, Kawanura T, et al. The liver as a crucial organ in the first line of host defense: the roles of Kupffer cells, natural killer (NK) cells and NK1.1 Ag + T cells in T helper 1 immune responses. Immunol Rev, 2000, 174: 35~46 [17] Chang D H, Osman K, Connolly J, et al. Sustained expansion of NKT cells and antigen-specific T cells after injection of α-galactosyl-ceramide loaded mature dendritic cells in cancer patients. J Exp Med, 2005, 201(9): 1503~1517 [18] Kawano T, Cui J Q, Koezuka Y, et al. Natural killer-like

5 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~ (Medical Research Council Technology) http: //

Σχετικά έγγραφα

ΠΑΝΕΠΙΣΤΗΜΙΟ ΙΩΑΝΝΙΝΩΝ ΑΝΟΙΚΤΑ ΑΚΑΔΗΜΑΪΚΑ ΜΑΘΗΜΑΤΑ

ΠΑΝΕΠΙΣΤΗΜΙΟ ΙΩΑΝΝΙΝΩΝ ΑΝΟΙΚΤΑ ΑΚΑΔΗΜΑΪΚΑ ΜΑΘΗΜΑΤΑ Παθοφυσιολογία ΙΙ Ογκολογία Υπεύθυνος μαθήματος: Καθηγητής Αλέξανδρος Α. Δρόσος Άδειες Χρήσης Το παρόν εκπαιδευτικό υλικό υπόκειται σε άδειες χρήσης Creative