Modulation of human dendritic-cell function following transduction with viral vectors: implications for gene therapy

Blood - Tập 105 Số 10 - Trang 3824-3832 - 2005
Peng Tan1,2,3,4, Sven C. Beutelspacher1,2,3,4, Shao‐An Xue1,2,3,4, Yaohe Wang1,2,3,4, Peter Mitchell1,2,3,4, James C. McAlister1,2,3,4, Frank Larkin1,2,3,4, Myra O. McClure1,2,3,4, Hans J. Stauss1,2,3,4, Mary A. Ritter1,2,3,4, Giovanna Lombardi1,2,3,4, Andrew J.T. George1,2,3,4
1From the Department of Immunology and the Cancer Research UK Molecular Oncology Unit, Division of Medicine, Faculty of Medicine, Imperial College London, Hammersmith Hospital; Jefferiss Research Trust Laboratories, Wright-Fleming Institute, Division of Medicine, Faculty of Medicine, Imperial College London, St Mary's Hospital; Moorfields Eye Hospital; and the Department of Molecular Genetics, Institute of Ophthalmology, University College London, London, United Kingdom.
2Jefferiss Research Trust Laboratories, Wright-Fleming Institute, Division of Medicine, Faculty of Medicine, Imperial College London, St Mary's Hospital
3Moorfields Eye Hospital
4the Department of Molecular Genetics, Institute of Ophthalmology, University College London, London, United Kingdom.

Tóm tắt

AbstractGenetic modification of dendritic-cell (DC) function is an attractive approach to treat disease, either using mature DCs (mDCs) to immunize patients, or immature DCs (iDCs) to induce tolerance. Viral vectors are efficient at transducing DCs, and we have investigated the effect of transduction with a variety of viral vectors on the phenotype and function of DCs. Adenovirus (Ad), human immunodeficiency virus (HIV), equine anemia virus (EIAV), and Moloney murine leukemia virus (MMLV) all up-regulate costimulatory molecules and major histocompatibility complex (MHC) class II expression on DCs, as well as, in the case of Ad and lentiviral vectors, inducing production of Th1 and proinflammatory cytokines. Following transduction there is activation of double-stranded (ds) RNA-triggered pathways resulting in interferon (IFN) α/β production. In addition, the function of virally infected DCs is altered; iDCs have an increased, and mDCs a decreased, ability to stimulate a mixed lymphocyte reaction (MLR). Viral transduction of mDCs results in up-regulation of the indoleamine 2,3-dioxygenase (IDO) enzyme, which down-regulates T-cell responsiveness. Inhibition of IDO restores the ability of mDCs to stimulate an MLR, indicating that IDO is responsible for the modulation of mDC function. These data have important implications for the use of viral vectors in the transduction of DCs.

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Tài liệu tham khảo

Banchereau J, Briere F, Caux C, et al. Immunobiology of dendritic cells. Annu Rev Immunol.2000; 18: 767-811.

Lechler R, Ng WF, Steinman RM. Dendritic cells in transplantation—friend or foe? Immunity.2001; 14: 357-368.

Thompson AG, Thomas R. Induction of immune tolerance by dendritic cells: implications for preventative and therapeutic immunotherapy of autoimmune disease. Immunol Cell Biol.2002;80: 509-519.

Ardavin C, Amigorena S, Reis e Sousa C. Dendritic cells: immunobiology and cancer immunotherapy. Immunity. 2004;20: 17-23.

Grohmann U, Fallarino F, Puccetti P. Tolerance, DCs and tryptophan: much ado about IDO. Trends Immunol.2003;24: 242-248.

Munn DH, Zhou M, Attwood JT, et al. Prevention of allogeneic fetal rejection by tryptophan catabolism. Science. 1998;281: 1191-1193.

Grohmann U, Orabona C, Fallarino F, et al. CTLA-4-Ig regulates tryptophan catabolism in vivo. Nat Immunol.2002;3: 1097-1101.

Fallarino F, Grohmann U, Hwang KW, et al. Modulation of tryptophan catabolism by regulatory T cells. Nat Immunol.2003;4: 1206-1212.

Diebold SS, Montoya M, Unger H, et al. Viral infection switches non-plasmacytoid dendritic cells into high interferon producers. Nature. 2003;424: 324-328.

Diebold SS, Kaisho T, Hemmi H, Akira S, Reis ESC. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science. 2004;303: 1529-1531.

Rea D, Schagen FH, Hoeben RC, et al. Adenoviruses activate human dendritic cells without polarization toward a T-helper type 1-inducing subset. J Virol.1999;73: 10245-10253.

Hirschowitz EA, Weaver JD, Hidalgo GE, Doherty DE. Murine dendritic cells infected with adenovirus vectors show signs of activation. Gene Ther.2000;7: 1112-1120.

Stark GR, Kerr IM, Williams BR, Silverman RH, Schreiber RD. How cells respond to interferons. Annu Rev Biochem.1998;67: 227-264.

Staeheli P, Grob R, Meier E, Sutcliffe JG, Haller O. Influenza virus-susceptible mice carry Mx genes with a large deletion or a nonsense mutation. Mol Cell Biol.1988;8: 4518-4523.

Patterson JB, Samuel CE. Expression and regulation by interferon of a double-stranded-RNA-specific adenosine deaminase from human cells: evidence for two forms of the deaminase. Mol Cell Biol.1995;15: 5376-5388.

Martensen PM, Sogaard TM, Gjermandsen IM, et al. The interferon alpha induced protein ISG12 is localized to the nuclear membrane. Eur J Biochem.2001;268: 5947-5954.

Nguyen LH, Espert L, Mechti N, Wilson DM 3rd. The human interferon- and estrogen-regulated ISG20/HEM45 gene product degrades single-stranded RNA and DNA in vitro. Biochemistry. 2001;40: 7174-7179.

Yuan W, Krug RM. Influenza B virus NS1 protein inhibits conjugation of the interferon (IFN)-induced ubiquitin-like ISG15 protein. Embo J.2001; 20: 362-371.

Zhou LJ, Tedder TF. CD14+ blood monocytes can differentiate into functionally mature CD83+ dendritic cells. Proc Natl Acad Sci U S A.1996;93: 2588-2592.

Bett AJ, Haddara W, Prevec L, Graham FL. An efficient and flexible system for construction of adenovirus vectors with insertions or deletions in early regions 1 and 3. Proc Natl Acad Sci U S A.1994;91: 8802-8806.

Naldini L, Blomer U, Gallay P, et al. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science. 1996;272: 263-267.

Bienemann AS, Martin-Rendon E, Cosgrave AS, et al. Long-term replacement of a mutated nonfunctional CNS gene: reversal of hypothalamic diabetes insipidus using an EIAV-based lentiviral vector expressing arginine vasopressin. Mol Ther.2003;7: 588-596.

Gruber A, Kan-Mitchell J, Kuhen KL, Mukai T, Wong-Staal F. Dendritic cells transduced by multiply deleted HIV-1 vectors exhibit normal phenotypes and functions and elicit an HIV-specific cytotoxic T-lymphocyte response in vitro. Blood. 2000;96: 1327-1333.

Pear WS, Nolan GP, Scott ML, Baltimore D. Production of high-titer helper-free retroviruses by transient transfection. Proc Natl Acad Sci U S A.1993;90: 8392-8396.

Lynch CM, Miller AD. Production of high-titer helper virus-free retroviral vectors by cocultivation of packaging cells with different host ranges. J Virol.1991;65: 3887-3890.

Miller AD, Garcia JV, von Suhr N, Lynch CM, Wilson C, Eiden MV. Construction and properties of retrovirus packaging cells based on gibbon ape leukemia virus. J Virol.1991;65: 2220-2224.

Dardalhon V, Jaleco S, Rebouissou C, et al. Highly efficient gene transfer in naive human T cells with a murine leukemia virus-based vector. Blood. 2000;96: 885-893.

Weijtens ME, Willemsen RA, Hart EH, Bolhuis RL. A retroviral vector system `STITCH' in combination with an optimized single chain antibody chimeric receptor gene structure allows efficient gene transduction and expression in human T lymphocytes. Gene Ther.1998;5: 1195-1203.

Demaison C, Parsley K, Brouns G, et al. High-level transduction and gene expression in hematopoietic repopulating cells using a human immunodeficiency [correction of imunodeficiency] virus type 1-based lentiviral vector containing an internal spleen focus forming virus promoter. Hum Gene Ther.2002;13: 803-813.

Tan PH, Manunta M, Ardjomand N, et al. Antibody targeted gene transfer to endothelium. J Gene Med.2003;5: 311-323.

Jordan WJ, Brookes PA, Szydlo RM, Goldman JM, Lechler RI, Ritter MA. IL-13 production by donor T cells is prognostic of acute graft-versus-host disease following unrelated donor stem cell transplantation. Blood. 2004;103: 717-724.

Marelli-Berg FM, Hargreaves RE, Carmichael P, Dorling A, Lombardi G, Lechler RI. Major histocompatibility complex class II-expressing endothelial cells induce allospecific nonresponsiveness in naive T cells. J Exp Med.1996;183: 1603-1612.

Tan PH, Chan C, Xue SA, et al. Phenotypic and functional differences between human saphenous vein (HSVEC) and umbilical vein (HUVEC) endothelial cells. Atherosclerosis. 2004;173: 171-183.

Xue SA, Lu QL, Poulsom R, Karran L, Jones MD, Griffin BE. Expression of two related viral early genes in Epstein-Barr virus-associated tumors. J Virol.2000;74: 2793-2803.

Harding HP, Zhang Y, Bertolotti A, Zeng H, Ron D. Perk is essential for translational regulation and cell survival during the unfolded protein response. Mol Cell.2000;5: 897-904.

Brewer JW, Diehl JA. PERK mediates cell-cycle exit during the mammalian unfolded protein response. Proc Natl Acad Sci U S A.2000;97: 12625-12630.

Takikawa O, Kuroiwa T, Yamazaki F, Kido R. Mechanism of interferon-gamma action: characterization of indoleamine 2,3-dioxygenase in cultured human cells induced by interferon-gamma and evaluation of the enzyme-mediated tryptophan degradation in its anticellular activity. J Biol Chem.1988;263: 2041-2048.

Uze G, Di Marco S, Mouchel-Vielh E, et al. Domains of interaction between alpha interferon and its receptor components. J Mol Biol.1994;243: 245-257.

Jonuleit H, Tuting T, Steitz J, et al. Efficient transduction of mature CD83+ dendritic cells using recombinant adenovirus suppressed T cell stimulatory capacity. Gene Ther.2000;7: 249-254.

Miller G, Lahrs S, Pillarisetty VG, Shah AB, DeMatteo RP. Adenovirus infection enhances dendritic cell immunostimulatory properties and induces natural killer and T-cell-mediated tumor protection. Cancer Res.2002;62: 5260-5266.

Philpott NJ, Nociari M, Elkon KB, Falck-Pedersen E. Adenovirus-induced maturation of dendritic cells through a PI3 kinase-mediated TNF-alpha induction pathway. Proc Natl Acad Sci U S A.2004;101: 6200-6205.

Negre D, Mangeot PE, Duisit G, et al. Characterization of novel safe lentiviral vectors derived from simian immunodeficiency virus (SIVmac251) that efficiently transduce mature human dendritic cells. Gene Ther.2000;7: 1613-1623.

Takayama T, Nishioka Y, Lu L, Lotze MT, Tahara H, Thomson AW. Retroviral delivery of viral interleukin-10 into myeloid dendritic cells markedly inhibits their allostimulatory activity and promotes the induction of T-cell hyporesponsiveness. Transplantation. 1998;66: 1567-1574.

Westermann J, Aicher A, Qin Z, et al. Retroviral interleukin-7 gene transfer into human dendritic cells enhances T cell activation. Gene Ther.1998;5: 264-271.

Akiyama Y, Watanabe M, Maruyama K, Ruscetti FW, Wiltrout RH, Yamaguchi K. Enhancement of antitumor immunity against B16 melanoma tumor using genetically modified dendritic cells to produce cytokines. Gene Ther.2000;7: 2113-2121.

Buonocore S, Van Meirvenne S, Demoor FX, et al. Dendritic cells transduced with viral interleukin 10 or Fas ligand: no evidence for induction of allotolerance in vivo. Transplantation. 2002;73: S27-S30.

Temme A, Morgenroth A, Schmitz M, et al. Efficient transduction and long-term retroviral expression of the melanoma-associated tumor antigen tyrosinase in CD34(+) cord blood-derived dendritic cells. Gene Ther.2002;9: 1551-1560.

Morelli AE, Larregina AT, Ganster RW, et al. Recombinant adenovirus induces maturation of dendritic cells via an NF-kappaB-dependent pathway. J Virol.2000;74: 9617-9628.

Andreakos E, Smith C, Monaco C, Brennan FM, Foxwell BM, Feldmann M. Ikappa B kinase 2 but not NF-kappa B-inducing kinase is essential for effective DC antigen presentation in the allogeneic mixed lymphocyte reaction. Blood. 2003; 101: 983-991.

Mackler AM, Barber EM, Takikawa O, Pollard JW. Indoleamine 2,3-dioxygenase is regulated by IFN-gamma in the mouse placenta during Listeria monocytogenes infection. J Immunol.2003;170: 823-830.

Yoshida R, Urade Y, Tokuda M, Hayaishi O. Induction of indoleamine 2,3-dioxygenase in mouse lung during virus infection. Proc Natl Acad Sci U S A.1979;76: 4084-4086.

Yoshida R, Hayaishi O. Induction of pulmonary indoleamine 2,3-dioxygenase by intraperitoneal injection of bacterial lipopolysaccharide. Proc Natl Acad Sci U S A.1978;75: 3998-4000.

Grohmann U, Fallarino F, Bianchi R, et al. IL-6 inhibits the tolerogenic function of CD8 alpha+ dendritic cells expressing indoleamine 2,3-dioxygenase. J Immunol.2001;167: 708-714.

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Blood

Tập 105 Số 10

3824-3832

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