Controlling cytomegalovirus: Helping the immune system take the lead

Viruses

Volumn 6, Issue 6, 2014, Pages 2242-2258

  Hanley, Patrick J ^a   Bollard, Catherine M ^a  

^a CHILDREN'S NATIONAL MEDICAL CENTER   (United States)

Author keywords

Adoptive immunotherapy; Cellular therapy; Cytomegalovirus (CMV); Immunotherapy; T cell; Transplant

Indexed keywords

CHEMOKINE RECEPTOR; INTERLEUKIN 10; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; LYMPHOCYTE ANTIGEN RECEPTOR;

ANTIGEN PRESENTING CELL; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL THERAPY; CYTOMEGALOVIRUS INFECTION; DOWN REGULATION; HUMAN; HUMORAL IMMUNITY; IMMUNE RESPONSE; IMMUNOGENICITY; INFECTION CONTROL; INNATE IMMUNITY; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); REVIEW; T LYMPHOCYTE; ANIMAL; CELLULAR IMMUNITY; CYTOMEGALOVIRUS; CYTOMEGALOVIRUS INFECTIONS; IMMUNE EVASION; IMMUNOLOGY; IMMUNOTHERAPY; METABOLISM; PHYSIOLOGY; T LYMPHOCYTE SUBPOPULATION; VIROLOGY;

ANIMALS; CYTOMEGALOVIRUS; CYTOMEGALOVIRUS INFECTIONS; HUMANS; IMMUNE EVASION; IMMUNITY, CELLULAR; IMMUNITY, HUMORAL; IMMUNITY, INNATE; IMMUNOTHERAPY; RECEPTORS, ANTIGEN, T-CELL; T-LYMPHOCYTE SUBSETS;

EID: 84901490222     PISSN: 19994915     EISSN: None     Source Type: Journal    
DOI: 10.3390/v6062242     Document Type: Review

References (101)

1. Cheung, A.K.; Gottlieb, D.J.; Plachter, B.; Pepperl-Klindworth, S.; Avdic, S.; Cunningham, A.L.; Abendroth, A.; Slobedman, B. The role of the human cytomegalovirus UL111A gene in down-regulating CD4+ T-cell recognition of latently infected cells: Implications for virus elimination during latency. Blood 2009, 114, 4128-4137.
2. Goodrum, F.D.; Jordan, C.T.; High, K.; Shenk, T. Human cytomegalovirus gene expression during infection of primary hematopoietic progenitor cells: A model for latency. Proc. Natl. Acad. Sci. USA 2002, 99, 16255-16260.
3. Reeves, M.B.; Sinclair, J.H. Analysis of latent viral gene expression in natural and experimental latency models of human cytomegalovirus and its correlation with histone modifications at a latent promoter. J. Gen. Virol. 2010, 91, 599-604.
4. Varnum, S.M.; Streblow, D.N. Monroe, M.E.; Smith, P.; Auberry, K.J.; Pasa-Tolic, L.; Wang, D.; Camp, D.G., Jr.; Rodland, K.; Wiley, S.; et al. Identification of proteins in human cytomegalovirus (HCMV) particles: The HCMV proteome. J. Virol. 2004, 78, 10960-10966.
5. Kalejta, R.F. Tegument proteins of human cytomegalovirus. Microbiol. Mol. Biol. Rev. 2008, 72, 249-265.
6. Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis; Arvin, A., Campadelli-Fiume, G., Mocarski, E., Moore, P.S., Roizman, B., Whitley, R., Yamanishi, K., Eds.; Cambridge University Press: Cambridge, UK, 2007.
7. Roby, C.; Gibson, W. Characterization of phosphoproteins and protein kinase activity of virions, noninfectious enveloped particles, and dense bodies of human cytomegalovirus. J. Virol. 1986, 59, 714-727.
8. Gandhi, M.K.; Khanna, R. Human cytomegalovirus: Clinical aspects, immune regulation, and emerging treatments. Lancet Infect. Dis. 2004, 4, 725-738.
9. Loewendorf, A.; Benedict, C.A. Modulation of host innate and adaptive immune defenses by cytomegalovirus: Timing is everything. J. Intern. Med. 2010, 267, 483-501.
10. Sissons, J.G.; Bain, M.; Wills, M.R. Latency and reactivation of human cytomegalovirus. J. Infect. 2002, 44, 73-77.
11. Paulus, C.; Nevels, M. The human cytomegalovirus major immediate-early proteins as antagonists of intrinsic and innate antiviral host responses. Viruses 2009, 1, 760-779.
12. Hahn, G.; Jores, R.; Mocarski, E.S. Cytomegalovirus remains latent in a common precursor of dendritic and myeloid cells. Proc. Natl. Acad. Sci. USA 1998, 95, 3937-3942.
13. Gerna, G.; Percivalle, E.; Lilleri, D.; Lozza, L.; Fornara, C.; Hahn, G.; Baldanti, F.; Revello, M.G. Dendritic-cell infection by human cytomegalovirus is restricted to strains carrying functional UL131-128 genes and mediates efficient viral antigen presentation to CD8+ T cells. J. Gen. Virol. 2005, 86, 275-284.
14. Fietze, E.; Prosch, S.; Reinke, P.; Stein, J.; Docke, W.D.; Staffa, G.; Löning, S.; Devaux, S.; Emmrich, F.; von Baehr, R. Cytomegalovirus infection in transplant recipients. The role of tumor necrosis factor. Transplantation 1994, 58, 675-680.
15. Bunde, T.; Kirchner, A.; Hoffmeister, B.; Habedank, D.; Hetzer, R.; Cherepnev, G.; Proesch, S.; Reinke, P.; Volk, H.D.; Lehmkuhl, H.; et al. Protection from cytomegalovirus after transplantation is correlated with immediate early 1-specific CD8 T cells. J. Exp. Med. 2005, 201, 1031-1036.
16. Kennedy-Nasser, A.A.; Bollard, C.M.; Myers, G.D.; Leung, K.S.; Gottschalk, S.; Zhang, Y.; Liu, H.; Heslop, H.E.; Brenner, M.K.; Krance, R.A. Comparable outcome of alternative donor and matched sibling donor hematopoietic stem cell transplant for children with acute lymphoblastic leukemia in first or second remission using alemtuzumab in a myeloablative conditioning regimen. Biol. Blood Marrow Transplant. 2008, 14, 1245-1252.
17. Mori, T.; Kato, J. Cytomegalovirus infection/disease after hematopoietic stem cell transplantation. Int. J. Hematol. 2010, 91, 588-595.
18. Boeckh, M.; Nichols, W.G. The impact of cytomegalovirus serostatus of donor and recipient before hematopoietic stem cell transplantation in the era of antiviral prophylaxis and preemptive therapy. Blood 2004, 103, 2003-2008.
19. Hanley, P.J.; Cruz, C.R.; Shpall, E.J.; Bollard, C.M. Improving clinical outcomes using adoptively transferred immune cells from umbilical cord blood. Cytotherapy 2010, 12, 713-720.
20. Ugarte-Torres, A.; Hoegh-Petersen, M.; Liu, Y.; Zhou, F.; Williamson, T.S.; Quinlan, D.; Sy, S.; Roa, L.; Khan, F.; Fonseca, K.; et al. Donor serostatus has an impact on cytomegalovirus-specific immunity, cytomegaloviral disease incidence, and survival in seropositive hematopoietic cell transplant recipients. Biol. Blood Marrow Transplant. 2011, 17, 574-585.
21. Jaskula, E.; Bochenska, J.; Kocwin, E.; Tarnowska, A.; Lange, A. CMV Serostatus of Donor-Recipient Pairs Influences the Risk of CMV Infection/Reactivation in HSCT Patients. Bone Marrow Res. 2012, 2012, 375075.
22. Falagas, M.E.; Paya, C.; Ruthazer, R.; Badley, A.; Patel, R.; Wiesner, R.; Griffith, J.; Freeman, R.; Rohrer, R.; Werner, B.G.; et al. Significance of cytomegalovirus for long-term survival after orthotopic liver transplantation: A prospective derivation and validation cohort analysis. Transplantation 1998, 66, 1020-1028.
23. Paya, C.V. Prevention of cytomegalovirus disease in recipients of solid-organ transplants. Clin. Infect. Dis. 2001, 32, 596-603.
24. Cope, A.V.; Sabin, C.; Burroughs, A.; Rolles, K.; Griffiths, P.D.; Emery, V.C. Interrelationships among quantity of human cytomegalovirus (HCMV) DNA in blood, donor-recipient serostatus, and administration of methylprednisolone as risk factors for HCMV disease following liver transplantation. J. Infect. Dis. 1997, 176, 1484-1490.
25. Sia, I.G.; Wilson, J.A.; Groettum, C.M.; Espy, M.J.; Smith, T.F.; Paya, C.V. Cytomegalovirus (CMV) DNA load predicts relapsing CMV infection after solid organ transplantation. J. Infect. Dis. 2000, 181, 717-720.
26. Boeckh, M. Current antiviral strategies for controlling cytomegalovirus in hematopoietic stem cell transplant recipients: Prevention and therapy. Transpl. Infect. Dis. 1999, 1, 165-178.
27. Shellam, G.R.; Allan, J.E.; Papadimitriou, J.M.; Bancroft, G.J. Increased susceptibility to cytomegalovirus infection in beige mutant mice. Proc. Natl. Acad. Sci. USA 1981, 78, 5104-5108.
28. Biron, C.A.; Byron, K.S.; Sullivan, J.L. Severe herpesvirus infections in an adolescent without natural killer cells. N. Engl. J. Med. 1989, 320, 1731-1735.
29. Iversen, A.C.; Norris, P.S.; Ware, C.F.; Benedict, C.A.; Human, N.K. Cells inhibit cytomegalovirus replication through a noncytolytic mechanism involving lymphotoxin-dependent induction of IFN-beta. J. Immunol. 2005, 175, 7568-7574.
30. Boehme, K.W.; Guerrero, M.; Compton, T. Human cytomegalovirus envelope glycoproteins B and H are necessary for TLR2 activation in permissive cells. J. Immunol. 2006, 177, 7094-7102.
31. Rossini, G.; Cerboni, C.; Santoni, A.; Landini, M.P.; Landolfo, S.; Gatti, D.; Gribaudo, G.; Varani, S. Interplay between human cytomegalovirus and intrinsic/innate host responses: A complex bidirectional relationship. Mediat. Inflamm. 2012, 2012, 607276.
32. Bratcher, D.F.; Bourne, N.; Bravo, F.J.; Schleiss, M.R.; Slaoui, M.; Myers, M.G.; Bernstein, D.I. Effect of passive antibody on congenital cytomegalovirus infection in guinea pigs. J. Infect. Dis. 1995, 172, 944-950.
33. Britt, W.J.; Vugler, L.; Butfiloski, E.J.; Stephens, E.B. Cell surface expression of human cytomegalovirus (HCMV) gp55-116 (gB): Use of HCMV-recombinant vaccinia virus-infected cells in analysis of the human neutralizing antibody response. J. Virol. 1990, 64, 1079-1085.
34. Gonczol, E.; deTaisne, C.; Hirka, G.; Berencsi, K.; Lin, W.C.; Paoletti, E.; Plotkin, S. High expression of human cytomegalovirus (HCMV)-gB protein in cells infected with a vaccinia-gB recombinant: The importance of the gB protein in HCMV immunity. Vaccine 1991, 9, 631-637.
35. Stagno, S.; Pass, R.F.; Cloud, G.; Britt, W.J.; Henderson, R.E.; Walton, P.D.; Veren, D.A.; Page, F.; Alford, C.A. Primary cytomegalovirus infection in pregnancy. Incidence, transmission to fetus, and clinical outcome. J. Am. Med. Assoc. (JAMA) 1986, 256, 1904-1908.
36. Revello, M.G.; Gerna, G. Diagnosis and management of human cytomegalovirus infection in the mother, fetus, and newborn infant. Clin. Microbiol. Rev. 2002, 15, 680-715.
37. Schleiss, M.R. Cytomegalovirus in the neonate: Immune correlates of infection and protection. Clin. Dev. Immunol. 2013, 2013, 501801.
38. Krause, P.R.; Bialek, S.R.; Boppana, S.B.; Griffiths, P.D.; Laughlin, C.A.; Ljungman, P.; Ljungman, P.; Mocarski, E.S.; Pass, R.F.; Read, J.S.; et al. Priorities for CMV vaccine development. Vaccine 2013, 32, 4-10.
39. Alonso Arias, R.; Moro-Garcia, M.A.; Echeverria, A.; Solano-Jaurrieta, J.J.; Suarez-Garcia, F.M.; Lopez-Larrea, C. Intensity of the humoral response to cytomegalovirus is associated with the phenotypic and functional status of the immune system. J. Virol. 2013, 87, 4486-4495.
40. Zhu, J.; Shearer, G.M.; Marincola, F.M.; Norman, J.E.; Rott, D.; Zou, J.P.; Epstein, S.E. Discordant cellular and humoral immune responses to cytomegalovirus infection in healthy blood donors: Existence of a Th1-type dominant response. Int. Immunol. 2001, 13, 785-790.
41. Landini, M.P.; Lazzarotto, T.; Xu, J.; Geballe, A.P.; Mocarski, E.S. Humoral immune response to proteins of human cytomegalovirus latency-associated transcripts. Biol. Blood Marrow Transplant. 2000, 6, 100-108.
42. Moss, P.; Rickinson, A. Cellular immunotherapy for viral infection after HSC transplantation. Nat. Rev. Immunol. 2005, 5, 9-20.
43. Crough, T.; Khanna, R. Immunobiology of human cytomegalovirus: From bench to bedside. Clin. Microbiol. Rev. 2009, 22, 76-98.
44. Olsson, J.; Wikby, A.; Johansson, B.; Lofgren, S.; Nilsson, B.O.; Ferguson, F.G. Age-related change in peripheral blood T-lymphocyte subpopulations and cytomegalovirus infection in the very old: The Swedish longitudinal OCTO immune study. Mech. Ageing Dev. 2000, 121, 187-201.
45. Spielmann, G.; Bollard, C.M.; Bigley, A.B.; Hanley, P.J.; Blaney, J.W.; Lavoy, E.C.; Pircher, H.; Simpson, R.J. The effects of age and latent cytomegalovirus infection on the redeployment of CD8+ T cell subsets in response to acute exercise in humans. Brain, Behav, Immunity 2013, doi:10.1016/j.bbi.2013.05.003.
46. Simpson, R.J.; Lowder, T.W.; Spielmann, G.; Bigley, A.B.; LaVoy, E.C.; Kunz, H. Exercise and the aging immune system. Ageing Res. Rev. 2012, 11, 404-420.
47. Reusser, P.; Riddell, S.R.; Meyers, J.D.; Greenberg, P.D. Cytotoxic T-lymphocyte response to cytomegalovirus after human allogeneic bone marrow transplantation: Pattern of recovery and correlation with cytomegalovirus infection and disease. Blood 1991, 78, 1373-1380.
48. Riddell, S.R.; Watanabe, K.S.; Goodrich, J.M.; Li, C.R.; Agha, M.E.; Greenberg, P.D. Restoration of viral immunity in immunodeficient humans by the adoptive transfer of T cell clones. Science 1992, 257, 238-241.
49. Sester, U.; Gartner, B.C.; Wilkens, H.; Schwaab, B.; Wossner, R.; Kindermann, I.; Girndt, M.; Meyerhans, A.; Mueller-Lantzsch, N.; Schäfers, H.J. Differences in CMV-specific T-cell levels and long-term susceptibility to CMV infection after kidney, heart and lung transplantation. Am. J. Transplant. 2005, 5, 1483-1489.
50. Radha, R.; Jordan, S.; Puliyanda, D.; Bunnapradist, S.; Petrosyan, A.; Amet, N.; Toyoda, M. Cellular immune responses to cytomegalovirus in renal transplant recipients. Am. J. Transplant. 2005, 5, 110-117.
51. Reusser, P.; Cathomas, G.; Attenhofer, R.; Tamm, M.; Thiel, G. Cytomegalovirus (CMV)-specific T cell immunity after renal transplantation mediates protection from CMV disease by limiting the systemic virus load. J. Infect. Dis. 1999, 180, 247-253.
52. Sester, M.; Sester, U.; Gartner, B.C.; Girndt, M.; Meyerhans, A.; Kohler, H. Dominance of virus-specific CD8 T cells in human primary cytomegalovirus infection. J. Am. Soc. Nephrol. (JASN) 2002, 13, 2577-2584.
53. Walter, E.A.; Greenberg, P.D.; Gilbert, M.J.; Finch, R.J.; Watanabe, K.S.; Thomas, E.D.; Riddell, S.R. Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor. N. Engl. J. Med. 1995, 333, 1038-1044.
54. Hanley, P.J.; Shaffer, D.R.; Cruz, C.R.; Ku, S.; Tzou, B.; Liu, H.; Demmler-Harrison, G.; Heslop, H.E.; Rooney, C.M.; Gottschalk, S.; et al. Expansion of T cells targeting multiple antigens of cytomegalovirus, Epstein-Barr virus and adenovirus to provide broad antiviral specificity after stem cell transplantation. Cytotherapy 2011, 13, 976-986.
55. Wills, M.R.; Carmichael, A.J.; Mynard, K.; Jin, X.; Weekes, M.P.; Plachter, B.; Sissons, J.G. The human cytotoxic T-lymphocyte (CTL) response to cytomegalovirus is dominated by structural protein pp65: Frequency, specificity, and T-cell receptor usage of pp65-specific CTL. J. Virol. 1996, 70, 7569-7579.
56. Sylwester, A.W.; Mitchell, B.L.; Edgar, J.B.; Taormina, C.; Pelte, C.; Ruchti, F.; Sleath, P.R.; Grabstein, K.H.; Hosken, N.A.; Kern, F.; et al. Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects. J. Exp. Med. 2005, 202, 673-685.
57. Polic, B.; Hengel, H.; Krmpotic, A.; Trgovcich, J.; Pavic, I.; Luccaronin, P.; Jonjić, S.; Koszinowski, U.H. Hierarchical and redundant lymphocyte subset control precludes cytomegalovirus replication during latent infection. J. Exp. Med. 1998, 188, 1047-1054.
58. Jonjic, S.; Pavic, I.; Lucin, P.; Rukavina, D.; Koszinowski, U.H. Efficacious control of cytomegalovirus infection after long-term depletion of CD8+ T lymphocytes. J. Virol. 1990, 64, 5457-5464.
59. Tu, W.; Chen, S.; Sharp, M.; Dekker, C.; Manganello, A.M.; Tongson, E.C.; Maecker, H.T.; Holmes, T.H.; Wang, Z.; Kemble, G.; et al. Persistent and selective deficiency of CD4+ T cell immunity to cytomegalovirus in immunocompetent young children. J. Immunol. 2004, 172, 3260-3267.
60. Antoine, P.; Olislagers, V.; Huygens, A.; Lecomte, S.; Liesnard, C.; Donner, C.; Marchant, A. Functional exhaustion of CD4+ T lymphocytes during primary cytomegalovirus infection. J. Immunol. 2012, 189, 2665-2672.
61. Einsele, H.; Roosnek, E.; Rufer, N.; Sinzger, C.; Riegler, S.; Loffler, J.; Grigoleit, U.; Moris, A.; Rammensee, H.G.; Kanzm L.; et al. Infusion of cytomegalovirus (CMV)-specific T cells for the treatment of CMV infection not responding to antiviral chemotherapy. Blood 2002, 99, 3916-3922.
62. Lehner, P.J.; Wilkinson, G.W. Cytomegalovirus: From evasion to suppression? Nat. Immunol. 2001, 2, 993-994.
63. Gilbert, M.J.; Riddell, S.R.; Plachter, B.; Greenberg, P.D. Cytomegalovirus selectively blocks antigen processing and presentation of its immediate-early gene product. Nature 1996, 383, 720-722.
64. Park, B.; Oh, H.; Lee, S.; Song, Y.; Shin, J.; Sung, Y.C.; Hwang, S.Y.; Ahn, K. The MHC class I homolog of human cytomegalovirus is resistant to down-regulation mediated by the unique short region protein (US)2, US3, US6, and US11 gene products. J. Immunol. 2002, 168, 3464-3469.
65. Miller, D.M.; Rahill, B.M.; Boss, J.M.; Lairmore, M.D.; Durbin, J.E.; Waldman, J.W.; Sedmak, D.D. Human cytomegalovirus inhibits major histocompatibility complex class II expression by disruption of the Jak/Stat pathway. J. Exp. Med. 1998, 187, 675-683.
66. Le Roy, E.; Muhlethaler-Mottet, A.; Davrinche, C.; Mach, B.; Davignon, J.L. Escape of human cytomegalovirus from HLA-DR-restricted CD4(+) T-cell response is mediated by repression of gamma interferon-induced class II transactivator expression. J. Virol. 1999, 73, 6582-6589.
67. Tomazin, R.; Boname, J.; Hegde, N.R.; Lewinsohn, D.M.; Altschuler, Y.; Jones, T.R.; Cresswell, P.; Nelson, J.A.; Riddell, S.R.; Johnson, D.C. Cytomegalovirus US2 destroys two components of the MHC class II pathway, preventing recognition by CD4+ T cells. Nat. Med. 1999, 5, 1039-1043.
68. Reyburn, H.T.; Mandelboim, O.; Vales-Gomez, M.; Davis, D.M.; Pazmany, L.; Strominger, J.L. The class I MHC homologue of human cytomegalovirus inhibits attack by natural killer cells. Nature 1997, 386, 514-517.
69. Wang, E.C.; McSharry, B.; Retiere, C.; Tomasec, P.; Williams, S.; Borysiewicz, L.K.; Braud, V.M.; Wilkinson, G.W. UL40-mediated NK evasion during productive infection with human cytomegalovirus. Proc. Natl. Acad. Sci. USA 2002, 99, 7570-7575.
70. Dunn, C.; Chalupny, N.J.; Sutherland, C.L.; Dosch, S.; Sivakumar, P.V.; Johnson, D.C.; Cosman, D. Human cytomegalovirus glycoprotein UL16 causes intracellular sequestration of NKG2D ligands, protecting against natural killer cell cytotoxicity. J. Exp. Med. 2003, 197, 1427-1439.
71. Casarosa, P.; Bakker, R.A.; Verzijl, D.; Navis, M.; Timmerman, H.; Leurs, R.; Martine, J.S. Constitutive signaling of the human cytomegalovirus-encoded chemokine receptor US28. J. Biol. Chem. 2001, 276, 1133-1137.
72. Skaletskaya, A.; Bartle, L.M.; Chittenden, T.; McCormick, A.L.; Mocarski, E.S.; Goldmacher, V.S. A cytomegalovirus-encoded inhibitor of apoptosis that suppresses caspase-8 activation. Proc. Natl. Acad. Sci. USA 2001, 98, 7829-7834.
73. Zhang, A.; Hildreth, R.L.; Colberg-Poley, A.M. Human cytomegalovirus inhibits apoptosis by proteasome-mediated degradation of Bax at endoplasmic reticulum-mitochondrion contacts. J. Virol. 2013, 87, 5657-5668.
74. Stern-Ginossar, N.; Elefant, N.; Zimmermann, A.; Wolf, D.G.; Saleh, N.; Biton, M.; Horwitz, E.; Prokocimer, Z.; Prichard, M.; Hahn, G.; et al. Host immune system gene targeting by a viral miRNA. Science 2007, 317, 376-381.
75. Stern-Ginossar, N.; Gur, C.; Biton, M.; Horwitz, E.; Elboim, M.; Stanietsky, N.; Mandelboim, M.; Mandelboim, O. Human microRNAs regulate stress-induced immune responses mediated by the receptor NKG2D. Nat. Immunol. 2008, 9, 1065-1073.
76. Mocarski, E.S., Jr. Immunomodulation by cytomegaloviruses: Manipulative strategies beyond evasion. Trends Microbiol. 2002, 10, 332-339.
77. Andrews, D.M.; Andoniou, C.E.; Granucci, F.; Ricciardi-Castagnoli, P.; Degli-Esposti, M.A. Infection of dendritic cells by murine cytomegalovirus induces functional paralysis. Nat. Immunol. 2001, 2, 1077-1084.
78. Noriega, V.; Redmann, V.; Gardner, T.; Tortorella, D. Diverse immune evasion strategies by human cytomegalovirus. Immunol. Res. 2012, 54, 140-151.
79. Miller-Kittrell, M.; Sparer, T.E. Feeling manipulated: Cytomegalovirus immune manipulation. Virol. J. 2009, 6, doi:10.1186/1743-422X-6-4.
80. Jackson, S.E.; Mason, G.M.; Wills, M.R. Human cytomegalovirus immunity and immune evasion. Virus Res. 2011, 157, 151-160.
81. Saglio, F.; Hanley, P.J.; Bollard, C.M. The time is now: Moving toward virus-specific T cells after allogeneic hematopoietic stem cell transplantation as the standard of care. Cytotherapy 2014, 16, 149-159.
82. Gerdemann, U.; Katari, U.L.; Papadopoulou, A.; Keirnan, J.M.; Craddock, J.A.; Liu, H.; Martinez, C.A.; Kennedy-Nasser, A.; Leung, K.S.; Gottschalk, S.M.; et al. Safety and clinical efficacy of rapidly-generated trivirus-directed T cells as treatment for adenovirus, EBV, and CMV infections after allogeneic hematopoietic stem cell transplant. Mol. Ther. 2013, 21, 2113-2121.
83. Leen, A.M.; Myers, G.D.; Sili, U.; Huls, M.H.; Weiss, H.; Leung, K.S.; Carrum, G.; Krance, R.A.; Chang, C.C.; Molldrem, J.J.; et al. Monoculture-derived T lymphocytes specific for multiple viruses expand and produce clinically relevant effects in immunocompromised individuals. Nat. Med. 2006, 12, 1160-1166.
84. Peggs, K.S.; Thomson, K.; Samuel, E.; Dyer, G.; Armoogum, J.; Chakraverty, R.; Pang, K.; Mackinnon, S.; Lowdell, M.W. Directly selected cytomegalovirus-reactive donor T cells confer rapid and safe systemic reconstitution of virus-specific immunity following stem cell transplantation. Clin. Infect. Dis. 2011, 52, 49-57.
85. Kroger, N.; Zabelina, T.; Kruger, W.; Renges, H.; Stute, N.; Schrum, J.; Kabisch, H.; Schafhausen, P.; Jaburg, N.; Löliger, C.; et al. Patient cytomegalovirus seropositivity with or without reactivation is the most important prognostic factor for survival and treatment-related mortality in stem cell transplantation from unrelated donors using pretransplant in vivo T-cell depletion with anti-thymocyte globulin. Br. J. Haematol. 2001, 113, 1060-1071.
86. Micklethwaite, K.P.; Clancy, L.; Sandher, U.; Hansen, A.M.; Blyth, E.; Antonenas, V.; Sartor, M.M.; Bradstock, K.F.; Gottlieb, D.J. Prophylactic infusion of cytomegalovirus-specific cytotoxic T lymphocytes stimulated with Ad5f35pp65 gene-modified dendritic cells after allogeneic hemopoietic stem cell transplantation. Blood 2008, 112, 3974-3981.
87. Cobbold, M.; Khan, N.; Pourgheysari, B.; Tauro, S.; McDonald, D.; Osman, H.; Assenmacher, M.; Billingham, L.; Colin. Adoptive transfer of cytomegalovirus-specific CTL to stem cell transplant patients after selection by HLA-peptide tetramers. J. Exp. Med. 2005, 202, 379-386.
88. Hanley, P.J.; Martinez, C.; Leung, K.; Savoldo, B.; Dotti, G.; Brenner, M.K.; Rooney, C.; Heslop, H.; Krance, R.; Shpall, E.J.; et al. Improving Immune Reconstitution after cord blood transplantation using ex vivo expanded virus-specific T cells: A phase I clinical study. ASH Annu. Meet. Abstr. 2013, 15, S21.
89. Blyth, E.; Clancy, L.; Simms, R.; Ma, C.K.; Burgess, J.; Deo, S.; Byth, K.; Dubosq, M.C.; Shaw, P.J.; Micklethwaite, K.P.; et al. Donor-derived CMV-specific T cells reduce the requirement for CMV-directed pharmacotherapy after allogeneic stem cell transplantation. Blood 2013, 121, 3745-3758.
90. Sun, Q.; Burton, R.L.; Pollok, K.E.; Emanuel, D.J.; Lucas, K.G. CD4(+) Epstein-Barr virus-specific cytotoxic T-lymphocytes from human umbilical cord blood. Cell. Immunol. 1999, 195, 81-88.
91. Savoldo, B.; Cubbage, M.L.; Durett, A.G.; Goss, J.; Huls, M.H.; Liu, Z.; Teresita, L.; Gee, A.P.; Ling, P.D.; Brenner, M.K.; et al. Generation of EBV-specific CD4+ cytotoxic T cells from virus naive individuals. J. Immunol. 2002, 168, 909-918.
92. Park, K.D.; Marti, L.; Kurtzberg, J.; Szabolcs, P. In vitro priming and expansion of cytomegalovirus-specific Th1 and Tc1 T cells from naive cord blood lymphocytes. Blood 2006, 108, 1770-1773.
93. Hanley, P.J.; Lam, S.; Shpall, E.J.; Bollard, C.M. Expanding cytotoxic T lymphocytes from umbilical cord blood that target cytomegalovirus, Epstein-Barr virus, and adenovirus. J. Vis. Exp. 2012, e3627, doi:10.3791/3627.
94. Hanley, P.J.; Cruz, C.R.; Savoldo, B.; Leen, A.M.; Stanojevic, M.; Khalil, M.; Decker, W.; Molldrem, J.J.; Liu, H.; Gee, A.P.; et al. Functionally active virus-specific T cells that target CMV, adenovirus, and EBV can be expanded from naive T-cell populations in cord blood and will target a range of viral epitopes. Blood 2009, 114, 1958-1967.
95. Jedema, I.; van de Meent, M.; Pots, J.; Kester, M.G.; van der Beek, M.T.; Falkenburg, J.H. Successful generation of primary virus-specific and anti-tumor T-cell responses from the naive donor T-cell repertoire is determined by the balance between antigen-specific precursor T cells and regulatory T cells. Haematologica 2011, 96, 1204-1212.
96. Hanley, P.J.; Cruz, R.Y.; Melenhorst, J.; Scheinberg, J.; Blaney, J.; Savoldo, B.; Dotti, G.; Heslop, H.; Rooney, C.M.; Shpall, E.J.; et al. Naive T-cell-derived CTL recognize atypical epitopes of CMVpp65 with higher avidity than CMV-seropositive donor-derived CTL-A basis for treatment of post-transplant viral infection by adoptive transfer of T-cells from virus-naive donors. Cytotherapy 2013, 15, S9.
97. Barker, J.N.; Doubrovina, E.; Sauter, C.; Jaroscak, J.J.; Perales, M.A.; Doubrovin, M.; Prockop, S.E.; Koehne, G.; O'Reilly, R.J. Successful treatment of EBV-associated posttransplantation lymphoma after cord blood transplantation using third-party EBV-specific cytotoxic T lymphocytes. Blood 2010, 116, 5045-5049.
98. Doubrovina, E.; Oflaz-Sozmen, B.; Prockop, S.E.; Kernan, N.A.; Abramson, S.; Teruya-Feldstein, J.; Hedvat, C.; Chou, J.F.; Heller, G.; Barker, J.N.; et al. Adoptive immunotherapy with unselected or EBV-specific T cells for biopsy-proven EBV+ lymphomas after allogeneic hematopoietic cell transplantation. Blood 2012, 119, 2644-2656.
99. Uhlin, M.; Okas, M.; Gertow, J.; Uzunel, M.; Brismar, T.B.; Mattsson, J. A novel haplo-identical adoptive CTL therapy as a treatment for EBV-associated lymphoma after stem cell transplantation. Cancer Immunol. Immunother. (CII) 2010, 59, 473-437.
100. Leen, A.M.; Bollard, C.M.; Mendizabal, A.M.; Shpall, E.J.; Szabolcs, P.; Antin, J.H.; Kapoor, N.; Pai, S.Y.; Rowley, S.D.; Kebriaei, P.; et al. Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation. Blood 2013, 121, 5113-5123.
101. Qasim, W.; Derniame, S.; Gilmour, K.; Chiesa, R.; Weber, M.; Adams, S.; Rao, K.; Amrolia, P.; Goulden, N. Third-party virus-specific T cells eradicate adenoviraemia but trigger bystander graft-versus-host disease. Br. J. Haematol. 2011, 154, 150-153.