Immune-mediated loss of transgene expression from virally transduced brain cells is irreversible, mediated by IFNγ, perforin, and TNFα, and due to the elimination of transduced cells

Molecular Therapy

Volumn 20, Issue 4, 2012, Pages 808-819

  Zirger, Jeffrey M ^a,b   Puntel, Mariana ^a,b   Bergeron, Josee ^a,b   Wibowo, Mia ^a,b   Moridzadeh, Rameen ^a,b   Bondale, Niyati ^a,b   Barcia, Carlos ^a,b   Kroeger, Kurt M ^a,b   Liu, Chunyan ^a,b   Castro, Maria G ^a,b,c   Lowenstein, Pedro R ^a,b,c  

^a CEDARS SINAI MEDICAL CENTER   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOVIRUS VECTOR; BETA GALACTOSIDASE; CRE RECOMBINASE; GAMMA INTERFERON; PERFORIN; THYMIDINE KINASE 1; TUMOR NECROSIS FACTOR ALPHA;

ADAPTIVE IMMUNITY; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIBODY LABELING; ARTICLE; BRAIN CELL; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CONFOCAL MICROSCOPY; CONTROLLED STUDY; CYTOTOXICITY; DOWN REGULATION; GENE EXPRESSION REGULATION; GENE INDUCTION; GENE THERAPY; IMMUNIZATION; IMMUNOHISTOCHEMISTRY; IMMUNOREACTIVITY; IMMUNOSUPPRESSIVE TREATMENT; LYMPHOCYTIC INFILTRATION; MOUSE; NONHUMAN; PHAGOCYTOSIS; SPLEEN CELL; TRANSGENE; VIRAL GENE DELIVERY SYSTEM;

ANIMALIA;

EID: 84862809425     PISSN: 15250016     EISSN: 15250024     Source Type: Journal    
DOI: 10.1038/mt.2011.243     Document Type: Article

References (50)

1. Thomas, CE, Schiedner, G, Kochanek, S, Castro, MG and Lenstein, PR (2000). Peripheral infection with adenovirus causes unexpected long-term brain inflammation in animals injected intracranially with first-generation, but not with high-capacity, adenovirus vectors: toward realistic long-term neurological gene therapy for chronic diseases. Proc Natl Acad Sci USA 97: 7482-7487. (Pubitemid 30431489)
2. Barcia, C, Jimenez-Dalmaroni, M, Kroeger, KM, Puntel, M, Rapaport, AJ, Larocque, D et al. (2007). One-year expression from high-capacity adenoviral vectors in the brains of animals with pre-existing anti-adenoviral immunity: clinical implications. Mol Ther 15: 2154-2163. (Pubitemid 350148932)
3. Barcia, C, Thomas, CE, Curtin, JF, King, GD, Wawrowsky, K, Candolfi, M et al. (2006). In vivo mature immunological synapses forming SMACs mediate clearance of virally infected astrocytes from the brain. J Exp Med 203: 2095-2107.
4. Määtta AM, Samaranayake, H, Pikkarainen, J, Wirth, T and YläHerttuala, S (2009). Adenovirus mediated herpes simplex virus-thymidine kinase/ganciclovir gene therapy for resectable malignant glioma. Curr Gene Ther 9: 356-367.
5. Wirth, T, Samaranayake, H, Pikkarainen, J, Määtta AM and YläHerttuala, S (2009). Clinical trials for glioblastoma multiforme using adenoviral vectors. Curr Opin Mol Ther 11: 485-492.
6. Pulkkanen, KJ and Yla-Herttuala, S (2005). Gene therapy for malignant glioma: current clinical status. Mol Ther 12: 585-598. (Pubitemid 41350140)
7. Asadi-Moghaddam, K and Chiocca, EA (2009). Gene-and viral-based therapies for brain tumors. Neurotherapeutics 6: 547-557.
8. Chiocca, EA, Abbed, KM, Tatter, S, Louis, DN, Hochberg, FH, Barker, F et al. (2004). A phase I open-label, dose-escalation, multi-institutional trial of injection with an E1B-Attenuated adenovirus, ONYX-015, into the peritumoral region of recurrent malignant gliomas, in the adjuvant setting. Mol Ther 10: 958-966. (Pubitemid 39419921)
9. Jiang, H, Gomez-Manzano, C, Lang, FF, Alemany, R and Fueyo, J (2009). Oncolytic adenovirus: preclinical and clinical studies in patients with human malignant gliomas. Curr Gene Ther 9: 422-427.
10. Jiang, H, Couto, LB, Patarroyo-White, S, Liu, T, Nagy, D, Vargas, JA et al. (2006). Effects of transient immunosuppression on adenoassociated, virus-mediated, liverdirected gene transfer in rhesus macaques and implications for human gene therapy. Blood 108: 3321-3328.
11. Lang, FF, Bruner, JM, Fuller, GN, Aldape, K, Prados, MD, Chang, S et al. (2003). Phase I trial of adenovirus-mediated p53 gene therapy for recurrent glioma: biological and clinical results. J Clin Oncol 21: 2508-2518. (Pubitemid 46606332)
12. Lowenstein, PR and Castro, MG (2009). Uncertainty in the translation of preclinical experiments to clinical trials. Why do most phase III clinical trials fail? Curr Gene Ther 9: 368-374.
13. Byrnes, AP, MacLaren, RE and Charlton, HM (1996). Immunological instability of persistent adenovirus vectors in the brain: peripheral exposure to vector leads to renewed inflammation, reduced gene expression, and demyelination. J Neurosci 16: 3045-3055. (Pubitemid 26121847)
14. Thomas, CE, Abordo-Adesida, E, Maleniak, TC, Stone, D, Gerdes, G and Lowenstein, PR. (2000). Gene transfer into rat brain using adenoviral vectors. In: Gerfen, JN, McKay, R, Rogawski, MA, Sibley, DR and Skolnick, P. (ed). Current Protocols in Neuroscience, vol. 4231-42340. Wiley: New York. pp. 242321-242340.
15. Byrnes, AP, Rusby, JE, Wood, MJ and Charlton, HM (1995). Adenovirus gene transfer causes inflammation in the brain. Neuroscience 66: 1015-1024.
16. Barcia, C, Sanderson, NS, Barrett, RJ, Wawrowsky, K, Kroeger, KM, Puntel, M et al. (2008). T cells' immunological synapses induce polarization of brain astrocytes in vivo and in vitro: a novel astrocyte response mechanism to cellular injury. PLoS ONE 3: e2977.
17. Barcia, C, et al. (2005). CD8 T cells are directly involved in silencing adenoviral vectorencoded transgene expression in the rat brain activated by systemic immune response. Society for Neuroscience Annual Meeting-Abstract. Mol Ther 11: S366-S366.
18. Barcia, C, Gerdes, C, Xiong, WD, Thomas, CE, Liu, C, Kroeger, KM et al. (2006). Immunological thresholds in neurological gene therapy: highly efficient elimination of transduced cells might be related to the specific formation of immunological synapses between T cells and virus-infected brain cells. Neuron Glia Biol 2: 309-322.
19. Huse, M, Lillemeier, BF, Kuhns, MS, Chen, DS and Davis, MM (2006). T cells use two directionally distinct pathways for cytokine secretion. Nat Immunol 7: 247-255.
20. O'Keefe, JP and Gajewski, TF (2005). Cutting edge: cytotoxic granule polarization and cytolysis can occur without central supramolecular activation cluster formation in CD8+ effector T cells. J Immunol 175: 5581-5585. (Pubitemid 41508034)
21. Shi, L, Keefe, D, Durand, E, Feng, H, Zhang, D and Lieberman, J (2005). Granzyme B binds to target cells mostly by charge and must be added at the same time as perforin to trigger apoptosis. J Immunol 174: 5456-5461. (Pubitemid 40593185)
22. McGavern, DB, Homann, D and Oldstone, MB (2002). T cells in the central nervous system: the delicate balance between viral clearance and disease. J Infect Dis 186 Suppl 2: S145-S151. (Pubitemid 35370474)
23. Griffin, DE (2010). Recovery from viral encephalomyelitis: immune-mediated noncytolytic virus clearance from neurons. Immunol Res 47: 123-133.
24. Diamond, MS, Mehlhop, E, Oliphant, T and Samuel, MA (2009). The host immunologic response to West Nile encephalitis virus. Front Biosci 14: 3024-3034.
25. Hausmann, J, Pagenstecher, A, Baur, K, Richter, K, Rziha, HJ and Staeheli, P (2005). CD8 T cells require gamma interferon to clear borna disease virus from the brain and prevent immune system-mediated neuronal damage. J Virol 79: 13509-13518. (Pubitemid 41508163)
26. Bantug, GR, Cekinovic, D, Bradford, R, Koontz, T, Jonjic, S and Britt, WJ (2008). CD8+ T lymphocytes control murine cytomegalovirus replication in the central nervous system of newborn animals. J Immunol 181: 2111-2123.
27. Glass, WG, Chen, BP, Liu, MT and Lane, TE (2002). Mouse hepatitis virus infection of the central nervous system: chemokine-mediated regulation of host defense and disease. Viral Immunol 15: 261-272. (Pubitemid 34651530)
28. Conrady, CD, Drevets, DA and Carr, DJ (2010). Herpes simplex type I (HSV-1) infection of the nervous system: is an immune response a good thing? J Neuroimmunol 220: 1-9.
29. Rall, GF, Mucke, L and Oldstone, MB (1995). Consequences of cytotoxic T lymphocyte interaction with major histocompatibility complex class I-expressing neurons in vivo. J Exp Med 182: 1201-1212.
30. Griffin, DE (2003). Immune responses to RNA-virus infections of the CNS. Nat Rev Immunol 3: 493-502. (Pubitemid 37339189)
31. Kanegae, Y, et al. (1995). Efficient gene activation in mammalian cells by using recombinant adenovirus expressing site-specific Cre recombinase. Nucleic Acids Res 23: 3816-3821.
32. Zambrowicz, BP, Imamoto, A, Fiering, S, Herzenberg, LA, Kerr, WG and Soriano, P (1997). Disruption of overlapping transcripts in the ROSA beta geo 26 gene trap strain leads to widespread expression of beta-galactosidase in mouse embryos and hematopoietic cells. Proc Natl Acad Sci USA 94: 3789-3794. (Pubitemid 27180451)
33. Ahmed, BY, Chakravarthy, S, Eggers, R, Hermens, WT, Zhang, JY, Niclou, SP et al. (2004). Efficient delivery of Cre-recombinase to neurons in vivo and stable transduction of neurons using adeno-associated and lentiviral vectors. BMC Neurosci 5: 4.
34. Wang, J, Xie, J, Lu, H, Chen, L, Hauck, B, Samulski, RJ et al. (2007). Existence of transient functional double-stranded DNA intermediates during recombinant AAV transduction. Proc Natl Acad Sci USA 104: 13104-13109. (Pubitemid 351737600)
35. Bergmann, CC, Parra, B, Hinton, DR, Ramakrishna, C, Dowdell, KC and Stohlman, SA (2004). Perforin and gamma interferon-mediated control of coronavirus central nervous system infection by CD8 T cells in the absence of CD4 T cells. J Virol 78: 1739-1750. (Pubitemid 38176706)
36. Williamson, JS and Stohlman, SA (1990). Effective clearance of mouse hepatitis virus from the central nervous system requires both CD4+ and CD8+ T cells. J Virol 64: 4589-4592. (Pubitemid 20279878)
37. Jiang, H, McCormick, F, Lang, FF, Gomez-Manzano, C and Fueyo, J (2006). Oncolytic adenoviruses as antiglioma agents. Expert Rev Anticancer Ther 6: 697-708. (Pubitemid 44192886)
38. Barcia, C, Wawrowsky, K, Barrett, RJ, Liu, C, Castro, MG and Lowenstein, PR (2008). In vivo polarization of IFN-gamma at Kupfer and non-Kupfer immunological synapses during the clearance of virally infected brain cells. J Immunol 180: 1344-1352.
39. Yang, J, Sanderson, NS, Wawrowsky, K, Puntel, M, Castro, MG and Lowenstein, PR (2010). Kupfer-type immunological synapse characteristics do not predict anti-brain tumor cytolytic T-cell function in vivo. Proc Natl Acad Sci USA 107: 4716-4721.
40. Lowenstein, PR, Mandel, RJ, Xiong, WD, Kroeger, K and Castro, MG (2007). Immune responses to adenovirus and adeno-associated vectors used for gene therapy of brain diseases: the role of immunological synapses in understanding the cell biology of neuroimmune interactions. Curr Gene Ther 7: 347-360. (Pubitemid 47595777)
41. Parra, B, Hinton, DR, Marten, NW, Bergmann, CC, Lin, MT, Yang, CS et al. (1999). IFN-gamma is required for viral clearance from central nervous system oligodendroglia. J Immunol 162: 1641-1647. (Pubitemid 29307040)
42. Southgate, TD, Bain, D, Fairbanks, LD, Morelli, AE, Larregina, AT, Simmonds, HA et al. (1999). Adenoviruses encoding HPRT correct biochemical abnormalities of HPRT-deficient cells and allow their survival in negative selection medium. Metab Brain Dis 14: 205-221. (Pubitemid 30337695)
43. Dewey, RA, Morrissey, G, Cowsill, CM, Stone, D, Bolognani, F, Dodd, NJ et al. (1999). Chronic brain inflammation and persistent herpes simplex virus 1 thymidine kinase expression in survivors of syngeneic glioma treated by adenovirus-mediated gene therapy: implications for clinical trials. Nat Med 5: 1256-1263. (Pubitemid 29535602)
44. Wilkinson, GW and Akrigg, A (1992). Constitutive and enhanced expression from the CMV major IE promoter in a defective adenovirus vector. Nucleic Acids Res 20: 2233-2239.
45. Southgate, T, Kroeger, KM, Liu, C, Lowenstein, PR, Castro, MG. (2008). Gene transfer into neural cells in vitro using adenoviral vectors. In: Jacqueline, NC et al. (eds). Current protocols in neuroscience. Wiley: Chichester, New York. ch. 4. pp. 242321-242343.
46. Ali, S, et al. (2005). Combined immunostimulation and conditional cytotoxic gene therapy provide long-term survival in a large glioma model. Cancer Res 65: 7194-7204. (Pubitemid 41161250)
47. Smith-Arica, JR, Morelli, AE, Larregina, AT, Smith, J, Lowenstein, PR and Castro, MG (2000). Cell-type-specific and regulatable transgenesis in the adult brain: adenovirusencoded combined transcriptional targeting and inducible transgene expression. Mol Ther 2: 579-587.
48. Paxinos, G and Watson, C (1986). The Rat Brain in Stereotaxic Coordinates. Academic press.
49. Chen, J, Hsu, HC, Zajac, AJ, Wu, Q, Yang, P, Xu, X et al. (2006). In vivo analysis of adenovirus-specific cytotoxic T lymphocyte response in mice deficient in CD28, fas ligand, and perforin. Hum Gene Ther 17: 669-682. (Pubitemid 43967870)
50. Puntel, M, Kroeger, KM, Sanderson, NS, Thomas, CE, Castro MG and Lowenstein, PR (2010). Gene transfer into rat brain using adenoviral vectors. In: Jacqueline, NC et al. (eds). Current Protocols in Neuroscience. ch. 4, pp. 241-2449.