#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Evaluating Human T-Cell Therapy of Cytomegalovirus Organ Disease in HLA-Transgenic Mice


Pre-emptive CD8 T-cell therapy of human cytomegalovirus (HCMV) disease in immunocompromised recipients of hematopoietic stem cell transplantation gave promising results in clinical trials, but limited efficacy and the need of HCMV-seropositive memory cell donors has so far prevented adoptive cell transfer from becoming clinical routine. Further development is currently hampered by the lack of experimental animal models that allow preclinical testing of the protective efficacy of human T cells in functional organs. While humanized mouse models with human tissue implants are technically and statistically demanding, and are limited to studying human T-cell activation and local virus control in the implants, a more feasible model for control of systemic infection and prevention of multiple-organ CMV disease is regrettably missing. Here we introduce such a model based on infection of genetically immunocompromised, HLA-A2.1-transgenic NOD/SCID/IL-2rg-/- mice with a chimeric murine CMV engineered to express the HCMV NLV-peptide epitope. Mimicking the scenario of HCMV-unexperienced donors, human T cells transduced with a human T-cell receptor specific for HLA-A.2.1-presented NLV peptide controlled systemic infection and moderated organ disease resulting in a survival benefit. The model promises to become instrumental in defining T-cell properties that determine their protective efficacy for a further development of adoptive immunotherapy of post-transplantation CMV infection.


Vyšlo v časopise: Evaluating Human T-Cell Therapy of Cytomegalovirus Organ Disease in HLA-Transgenic Mice. PLoS Pathog 11(7): e32767. doi:10.1371/journal.ppat.1005049
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005049

Souhrn

Pre-emptive CD8 T-cell therapy of human cytomegalovirus (HCMV) disease in immunocompromised recipients of hematopoietic stem cell transplantation gave promising results in clinical trials, but limited efficacy and the need of HCMV-seropositive memory cell donors has so far prevented adoptive cell transfer from becoming clinical routine. Further development is currently hampered by the lack of experimental animal models that allow preclinical testing of the protective efficacy of human T cells in functional organs. While humanized mouse models with human tissue implants are technically and statistically demanding, and are limited to studying human T-cell activation and local virus control in the implants, a more feasible model for control of systemic infection and prevention of multiple-organ CMV disease is regrettably missing. Here we introduce such a model based on infection of genetically immunocompromised, HLA-A2.1-transgenic NOD/SCID/IL-2rg-/- mice with a chimeric murine CMV engineered to express the HCMV NLV-peptide epitope. Mimicking the scenario of HCMV-unexperienced donors, human T cells transduced with a human T-cell receptor specific for HLA-A.2.1-presented NLV peptide controlled systemic infection and moderated organ disease resulting in a survival benefit. The model promises to become instrumental in defining T-cell properties that determine their protective efficacy for a further development of adoptive immunotherapy of post-transplantation CMV infection.


Zdroje

1. Boeckh M, Leisenring W, Riddell SR, Bowden RA, Huang M, Myerson D et al. (2003) Late cytomegalovirus disease and mortality in recipients of allogeneic hematopoietic stem cell transplants: importance of viral load and T-cell immunity. Blood 101: 407–414. 12393659

2. Ozdemir E, Saliba RM, Champlin RE, Couriel DR, Giralt SA, de Lima M et al. (2007) Risk factors associated with late cytomegalovirus reactivation after allogeneic stem cell transplantation for hematological malignancies. Bone Marrow Transplant 40: 125–136. 17530009

3. Reddehase MJ, Weiland F, Munch K, Jonjic S, Luske A, Koszinowski UH (1985) Interstitial murine cytomegalovirus pneumonia after irradiation: characterization of cells that limit viral replication during established infection of the lungs. J Virol 55: 264–273. 2991554

4. Steffens HP, Kurz S, Holtappels R, Reddehase MJ (1998) Preemptive CD8 T-cell immunotherapy of acute cytomegalovirus infection prevents lethal disease, limits the burden of latent viral genomes, and reduces the risk of virus recurrence. J Virol 72: 1797–1804. 9499030

5. Holtappels R, Podlech J, Grzimek NK, Thomas D, Pahl-Seibert MF, Reddehase MJ (2001) Experimental preemptive immunotherapy of murine cytomegalovirus disease with CD8 T-cell lines specific for ppM83 and pM84, the two homologs of human cytomegalovirus tegument protein ppUL83 (pp65). J Virol 75: 6584–6600. 11413326

6. Pahl-Seibert M, Juelch M, Podlech J, Thomas D, Deegen P, Reddehase MJ et al. (2005) Highly protective in vivo function of cytomegalovirus IE1 epitope-specific memory CD8 T cells purified by T-cell receptor-based cell sorting. J Virol 79: 5400–5413. 15827154

7. Holtappels R, Böhm V, Podlech J, Reddehase MJ (2008) CD8 T-cell-based immunotherapy of cytomegalovirus infection: "proof of concept" provided by the murine model. Med Microbiol Immunol 197: 125–134. doi: 10.1007/s00430-008-0093-2 18343947

8. Ebert S, Podlech J, Gillert-Marien D, Gergely KM, Büttner JK, Fink A et al. (2012) Parameters determining the efficacy of adoptive CD8 T-cell therapy of cytomegalovirus infection. Med Microbiol Immunol 201: 527–539. doi: 10.1007/s00430-012-0258-x 22972232

9. Holtappels R, Ebert S, Podlech J, Fink A, Böhm V, Lemmermann NA et al. (2013) Murine model for cytoimmunotherapy of CMV disease after haematopoietic cell transplantation. In: Reddehase MJ, ed. Cytomegaloviruses: From Molecular Pathogenesis to Intervention. Vol 2. Norfolk, UK: Caister Academic Press. pp. 354–381.

10. Riddell SR, Watanabe KS, Goodrich JM, Li CR, Agha ME, Greenberg PD (1992) Restoration of viral immunity in immunodeficient humans by the adoptive transfer of T cell clones. Science 257: 238–241. 1352912

11. Cobbold M, Khan N, Pourgheysari B, Tauro S, McDonald D, Osman H et al. (2005) Adoptive transfer of cytomegalovirus-specific CTL to stem cell transplant patients after selection by HLA-peptide tetramers. J Exp Med 202: 379–386. 16061727

12. Feuchtinger T, Opherk K, Bethge WA, Topp MS, Schuster FR, Weissinger EM et al. (2010) Adoptive transfer of pp65-specific T cells for the treatment of chemorefractory cytomegalovirus disease or reactivation after haploidentical and matched unrelated stem cell transplantation. Blood 116: 4360–4367. doi: 10.1182/blood-2010-01-262089 20625005

13. Thomas S, Herr W (2011) Natural and adoptive T-cell immunity against herpes family viruses after allogeneic hematopoietic stem cell transplantation. Immunotherapy 3: 771–788. doi: 10.2217/imt.11.47 21668314

14. Sellar RS, Peggs KS (2012) Therapeutic strategies for the prevention and treatment of cytomegalovirus infection. Expert Opin Biol Ther 12: 1161–1172. doi: 10.1517/14712598.2012.693471 22650422

15. Schub A, Schuster IG, Hammerschmidt W, Moosmann A (2009) CMV-specific TCR-transgenic T cells for immunotherapy. J Immunol 183: 6819–6830. doi: 10.4049/jimmunol.0902233 19864595

16. Thomas S, Klobuch S, Besold K, Plachter B, Dorrie J, Schaft N et al. (2012) Strong and sustained effector function of memory- versus naive-derived T cells upon T-cell receptor RNA transfer: implications for cellular therapy. Eur J Immunol 42: 3442–3453. doi: 10.1002/eji.201242666 22930221

17. Smith MG (1956) Propagation in tissue cultures of a cytopathogenic virus from human salivary gland virus (SGV) disease. Proc Soc Exp Biol Med 92: 424–430. 13350368

18. Brune W (2013) Molecular basis of cytomegalovirus host species specificity. In: Reddehase MJ, ed. Cytomegaloviruses: from molecular pathogenesis to intervention. Vol 1. Norfolk, UK: Caister Academic Press. pp. 322–329.

19. Mocarski ES, Bonyhadi M, Salimi S, McCune JM, Kaneshima H (1993) Human cytomegalovirus in a SCID-hu mouse: thymic epithelial cells are prominent targets of viral replication. Proc Natl Acad Sci USA 90: 104–108. 7678330

20. Brown JM, Kaneshima H, Mocarski ES (1995) Dramatic interstrain differences in the replication of human cytomegalovirus in SCID-hu mice. J Infect Dis 171: 1599–1603. 7769298

21. Bidanset DJ, Rybak RJ, Hartline CB, Kern ER (2001) Replication of human cytomegalovirus in severe combined immunodeficient mice implanted with human retinal tissue. J Infect Dis 184: 192–195. 11424017

22. Kern ER (2006) Pivotal role of animal models in the development of new therapies for cytomegalovirus infections. Antiviral Res 71: 164–171. 16828175

23. Kawahara T, Lisboa LF, Cader S, Douglas DN, Nourbakhsh M, Pu CH et al. (2013) Human cytomegalovirus infection in humanized liver chimeric mice. Hepatol Res 43: 679–684. doi: 10.1111/j.1872-034X.2012.01116.x 23442000

24. Smith MS, Streblow DN, Caposio P, Nelson JA (2013) Humanized mouse models of cytomegalovirus pathogenesis and latency. In Reddehase MJ, ed. Cytomegaloviruses: from molecular pathogenesis to intervention. Vol 1. Norfolk, UK: Caister Academic Press. pp. 417–436.

25. Smith MS, Goldman DC, Bailey AS, Pfaffle DL, Kreklywich CN, Spencer DB et al. (2010) Granulocyte-colony stimulating factor reactivates human cytomegalovirus in a latently infected humanized mouse model. Cell Host Microbe 8: 284–291. doi: 10.1016/j.chom.2010.08.001 20833379

26. Wills MR, Carmichael AJ, Mynard K, Jin X, Weekes MP, Plachter B et al. (1996) 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 70: 7569–7579. 8892876

27. Shultz LD, Saito Y, Najima Y, Tanaka S, Ochi T, Tomizawa M et al. (2010) Generation of functional human T-cell subsets with HLA-restricted immune responses in HLA class I expressing NOD/SCID/IL2r gamma(null) humanized mice. Proc Natl Acad Sci USA 107: 13022–13027. doi: 10.1073/pnas.1000475107 20615947

28. Giri JG, Ahdieh M, Eisenman J, Shanebeck K, Grabstein K, Kumaki S et al. (1994) Utilization of the beta and gamma chains of the IL-2 receptor by the novel cytokine IL-15. EMBO J 13: 2822–2830. 8026467

29. Anderson DM, Kumaki S, Ahdieh M, Bertles J, Tometsko M, Loomis A et al. (1995) Functional characterization of the human interleukin-15 receptor alpha chain and close linkage of IL15RA and IL2RA genes. J Biol Chem 270: 29862–29869. 8530383

30. Vidal S, Krmpotić A, Pyzik M, Jonjić S (2013) Innate immunity to cytomegalovirus in the murine model. In: Reddehase MJ, ed. Cytomegaloviruses: from molecular pathogenesis to intervention. Vol 2. Norfolk, UK: Caister Academic Press. pp. 192–214.

31. Lemmermann NA, Kropp KA, Seckert CK, Grzimek, Natascha K A, Reddehase MJ (2011) Reverse genetics modification of cytomegalovirus antigenicity and immunogenicity by CD8 T-cell epitope deletion and insertion. J Biomed Biotechnol 2011: 812742. doi: 10.1155/2011/812742 21253509

32. Ebert S, Lemmermann NA, Thomas D, Renzaho A, Reddehase MJ, Holtappels R (2012) Immune control in the absence of immunodominant epitopes: implications for immunotherapy of cytomegalovirus infection with antiviral CD8 T cells. Med Microbiol Immunol 201: 541–550. doi: 10.1007/s00430-012-0268-8 22976556

33. Messerle M, Keil GM, Koszinowski UH (1991) Structure and expression of murine cytomegalovirus immediate-early gene 2. J Virol 65: 1638–1643. 1847480

34. Cardin RD, Abenes GB, Stoddart CA, Mocarski ES (1995) Murine cytomegalovirus IE2, an activator of gene expression, is dispensable for growth and latency in mice. Virology 209: 236–241. 7747475

35. Grzimek NK, Dreis D, Schmalz S, Reddehase MJ (2001) Random, asynchronous, and asymmetric transcriptional activity of enhancer-flanking major immediate-early genes ie1/3 and ie2 during murine cytomegalovirus latency in the lungs. J Virol 75: 2692–2705. 11222693

36. Lemmermann NA, Krmpotic A, Podlech J, Brizic I, Prager A, Adler H et al. (2015) Non-redundant and redundant roles of cytomegalovirus gH/gL complexes in host organ entry and intra-tissue spread. PLoS Pathog 11: e1004640. doi: 10.1371/journal.ppat.1004640 25659098

37. Podlech J, Reddehase MJ, Adler B, Lemmermann NA (2015) Principles for studying in vivo attenuation of virus mutants: defining the role of the cytomegalovirus gH/gL/gO complex as a paradigm. Med Microbiol Immunol. 2015 Mar 18. [Epub ahead of print]

38. Besold K, Frankenberg N, Pepperl-Klindworth S, Kuball J, Theobald M, Hahn G et al. (2007) Processing and MHC class I presentation of human cytomegalovirus pp65-derived peptides persist despite gpUS2-11-mediated immune evasion. J Gen Virol 88: 1429–1439. 17412970

39. Obar JJ, Lefrancois L (2010) Memory CD8+ T cell differentiation. Ann N Y Acad Sci 1183: 251–266. doi: 10.1111/j.1749-6632.2009.05126.x 20146720

40. Obar JJ, Lefrancois L (2010) Early events governing memory CD8+ T-cell differentiation. Int Immunol 22: 619–625. doi: 10.1093/intimm/dxq053 20504887

41. Seckert CK, Griessl M, Büttner JK, Scheller S, Simon CO, Kropp KA et al. (2012) Viral latency drives 'memory inflation': a unifying hypothesis linking two hallmarks of cytomegalovirus infection. Med Microbiol Immunol 201: 551–566. doi: 10.1007/s00430-012-0273-y 22991040

42. Seckert CK, Griessl M, Büttner JK, Freitag K, Lemmermann NA, Hummel MA et al. (2013) Immune surveillance of cytomegalovirus latency and reactivation in murine models: link to ‘memory inflation’. In: Reddehase MJ, ed. Cytomegaloviruses: from molecular pathogenesis to intervention. Vol 1. Norfolk, UK: Caister Academic Press. pp. 374–416.

43. Zhou F (2009) Molecular mechanisms of IFN-gamma to up-regulate MHC class I antigen processing and presentation. Int Rev Immunol 28: 239–260. doi: 10.1080/08830180902978120 19811323

44. Holmberg K, Mariathasan S, Ohteki T, Ohashi PS, Gascoigne, Nicholas R J (2003) TCR binding kinetics measured with MHC class I tetramers reveal a positive selecting peptide with relatively high affinity for TCR. J Immunol 171: 2427–2434. 12928390

45. Kuball J, Schmitz FW, Voss R, Ferreira EA, Engel R, Guillaume P et al. (2005) Cooperation of human tumor-reactive CD4+ and CD8+ T cells after redirection of their specificity by a high-affinity p53A2.1-specific TCR. Immunity 22: 117–129. 15664164

46. Nauerth M, Weissbrich B, Knall R, Franz T, Dossinger G, Bet J et al. (2013) TCR-ligand koff rate correlates with the protective capacity of antigen-specific CD8+ T cells for adoptive transfer. Sci Transl Med 5: 192ra87. doi: 10.1126/scitranslmed.3005958 23825303

47. Hengel H, Lucin P, Jonjic S, Ruppert T, Koszinowski UH (1994) Restoration of cytomegalovirus antigen presentation by gamma interferon combats viral escape. J Virol 68: 289–297. 8254740

48. Fink A, Lemmermann NA, Gillert-Marien D, Thomas D, Freitag K, Böhm V et al. (2012) Antigen presentation under the influence of 'immune evasion' proteins and its modulation by interferon-gamma: implications for immunotherapy of cytomegalovirus infection with antiviral CD8 T cells. Med Microbiol Immunol 201: 513–525. doi: 10.1007/s00430-012-0256-z 22961126

49. Lemmermann NA, Fink A, Podlech J, Ebert S, Wilhelmi V, Böhm V et al. (2012) Murine cytomegalovirus immune evasion proteins operative in the MHC class I pathway of antigen processing and presentation: state of knowledge, revisions, and questions. Med Microbiol Immunol 201: 497–512. doi: 10.1007/s00430-012-0257-y 22961127

50. Wagner M, Gutermann A, Podlech J, Reddehase MJ, Koszinowski UH (2002) Major histocompatibility complex class I allele-specific cooperative and competitive interactions between immune evasion proteins of cytomegalovirus. J Exp Med 196: 805–816. 12235213

51. Holtappels R, Gillert-Marien D, Thomas D, Podlech J, Deegen P, Herter S et al. (2006) Cytomegalovirus encodes a positive regulator of antigen presentation. J Virol 80: 7613–7624. 16840340

52. Alterio de Goss M, Holtappels R, Steffens HP, Podlech J, Angele P, Dreher L et al. (1998) Control of cytomegalovirus in bone marrow transplantation chimeras lacking the prevailing antigen-presenting molecule in recipient tissues rests primarily on recipient-derived CD8 T cells. J Virol 72: 7733–7744. 9733809

53. Podlech J, Holtappels R, Pahl-Seibert MF, Steffens HP, Reddehase MJ (2000) Murine model of interstitial cytomegalovirus pneumonia in syngeneic bone marrow transplantation: persistence of protective pulmonary CD8-T-cell infiltrates after clearance of acute infection. J Virol 74: 7496–7507. 10906203

54. Böhm V, Podlech J, Thomas D, Deegen P, Pahl-Seibert M, Lemmermann NA et al. (2008) Epitope-specific in vivo protection against cytomegalovirus disease by CD8 T cells in the murine model of preemptive immunotherapy. Med Microbiol Immunol 197: 135–144. doi: 10.1007/s00430-008-0092-3 18340461

55. Sacher T, Podlech J, Mohr CA, Jordan S, Ruzsics Z, Reddehase MJ et al. (2008) The major virus-producing cell type during murine cytomegalovirus infection, the hepatocyte, is not the source of virus dissemination in the host. Cell Host Microbe 3: 263–272. doi: 10.1016/j.chom.2008.02.014 18407069

56. Stahl FR, Heller K, Halle S, Keyser KA, Busche A, Marquardt A et al. (2013) Nodular inflammatory foci are sites of T cell priming and control of murine cytomegalovirus infection in the neonatal lung. PLoS Pathog 9: e1003828. doi: 10.1371/journal.ppat.1003828 24348257

57. Ebert S, Becker M, Lemmermann NA, Büttner JK, Michel A, Taube C et al. (2014) Mast cells expedite control of pulmonary murine cytomegalovirus infection by enhancing the recruitment of protective CD8 T cells to the lungs. PLoS Pathog 10: e1004100. doi: 10.1371/journal.ppat.1004100 24763809

58. Boeckh M, Nichols WG (2004) The impact of cytomegalovirus serostatus of donor and recipient before hematopoietic stem cell transplantation in the era of antiviral prophylaxis and preemptive therapy. Blood 103: 2003–2008. 14644993

59. Zhou W, Longmate J, Lacey SF, Palmer JM, Gallez-Hawkins G, Thao L et al. (2009) Impact of donor CMV status on viral infection and reconstitution of multifunction CMV-specific T cells in CMV-positive transplant recipients. Blood 113: 6465–6476. doi: 10.1182/blood-2009-02-203307 19369230

60. Borchers S, Luther S, Lips U, Hahn N, Kontsendorn J, Stadler M et al. (2011) Tetramer monitoring to assess risk factors for recurrent cytomegalovirus reactivation and reconstitution of antiviral immunity post allogeneic hematopoietic stem cell transplantation. Transpl Infect Dis 13: 222–236. doi: 10.1111/j.1399-3062.2011.00626.x 21585633

61. Ugarte-Torres A, Hoegh-Petersen M, Liu Y, Zhou F, Williamson TS, Quinlan D et al. (2011) Donor serostatus has an impact on cytomegalovirus-specific immunity, cytomegaloviral disease incidence, and survival in seropositive hematopoietic cell transplant recipients. Biol Blood Marrow Transplant 17: 574–585. doi: 10.1016/j.bbmt.2010.07.020 20688181

62. Eiz-Vesper B, Maecker-Kolhoff B, Blasczyk R (2012) Adoptive T-cell immunotherapy from third-party donors: characterization of donors and set up of a T-cell donor registry. Front Immunol 3: 410. doi: 10.3389/fimmu.2012.00410 23372567

63. Stemberger C, Graef P, Odendahl M, Albrecht J, Dossinger G, Anderl F et al. (2014) Lowest numbers of primary CD8(+) T cells can reconstitute protective immunity upon adoptive immunotherapy. Blood 124: 628–637. doi: 10.1182/blood-2013-12-547349 24855206

64. Kershaw MH, Westwood JA, Darcy PK (2013) Gene-engineered T cells for cancer therapy. Nat Rev Cancer 13: 525–541. doi: 10.1038/nrc3565 23880905

65. Rosenberg SA, Restifo NP (2015) Adoptive cell transfer as personalized immunotherapy for human cancer. Science 348: 62–68. doi: 10.1126/science.aaa4967 25838374

66. Besold K, Wills M, Plachter B (2009) Immune evasion proteins gpUS2 and gpUS11 of human cytomegalovirus incompletely protect infected cells from CD8 T cell recognition. Virology 391: 5–19. doi: 10.1016/j.virol.2009.06.004 19570562

67. Li Y, Kurlander RJ (2010) Comparison of anti-CD3 and anti-CD28-coated beads with soluble anti-CD3 for expanding human T cells: differing impact on CD8 T cell phenotype and responsiveness to restimulation. J Transl Med 8: 104. doi: 10.1186/1479-5876-8-104 20977748

68. Kunert A, Straetemans T, Govers C, Lamers C, Mathijssen R, Sleijfer S et al. (2013) TCR-Engineered T Cells Meet New Challenges to Treat Solid Tumors: Choice of Antigen, T Cell Fitness, and Sensitization of Tumor Milieu. Front Immunol 4: 363. doi: 10.3389/fimmu.2013.00363 24265631

69. Barrett DM, Singh N, Liu X, Jiang S, June CH, Grupp SA et al. (2014) Relation of clinical culture method to T-cell memory status and efficacy in xenograft models of adoptive immunotherapy. Cytotherapy 16: 619–630. doi: 10.1016/j.jcyt.2013.10.013 24439255

70. Cieri N, Mastaglio S, Oliveira G, Casucci M, Bondanza A, Bonini C (2014) Adoptive immunotherapy with genetically modified lymphocytes in allogeneic stem cell transplantation. Immunol Rev 257: 165–180. doi: 10.1111/imr.12130 24329796

71. Ghazal P, Messerle M, Osborn K, Angulo A (2003) An essential role of the enhancer for murine cytomegalovirus in vivo growth and pathogenesis. J Virol 77: 3217–3228. 12584345

72. Handke W, Krause E, Brune W (2012) Live or let die: manipulation of cellular suicide programs by murine cytomegalovirus. Med Microbiol Immunol 201: 475–486. doi: 10.1007/s00430-012-0264-z 22965170

73. McCormick AL, Macarski ES (2013) Cell death pathways controlled by cytomegalovirus. In: Reddehase MJ, ed. Cytomegaloviruses: from molecular pathogenesis to intervention. Vol 1. Norfolk, UK: Caister Academic Press. pp. 264–277.

74. Arapovic J, Arapovic M, Golemac M, Traven L, Tomac J, Rumora D et al. (2015) The specific NK cell response in concert with perforin prevents CD8 T cell-mediated immunopathology after mouse cytomegalovirus infection. Med Microbiol Immunol. 2015 Mar 26. [Epub ahead of print]

75. Allen LB, Li SX, Arnett G, Toyer B, Shannon WM, Hollingshead MG (1992) Novel method for evaluating antiviral drugs against human cytomegalovirus in mice. Antimicrob Agents Chemother 36: 206–208. 1317146

76. Pari GS, Netski D, St Jeor S, McCarthy D, Smith J, Georgio D et al. (1998) Generation of a nude mouse tumor model for in vivo replication of human cytomegalovirus. J Infect Dis 177: 523–528. 9498427

77. Sylwester AW, Mitchell BL, Edgar JB, Taormina C, Pelte C, Ruchti F et al. (2005) Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects. J Exp Med 202: 673–685. 16147978

78. Wills MR, Mason GM, Sissons JG (2013) Adaptive cellular immunity to human cytomegalovirus. In: Reddehase MJ, ed. Cytomegalovirus: from molecular pathogenesis to intervention. Vol 2. Norfolk, UK: Caister Academic Press. pp. 142–176.

79. Sissons JG, Wills MR (2015) How understanding immunology contributes to managing CMV disease in immunosuppressed patients: now and in future. Med Microbiol Immunol. 2015 Apr 21. [Epub ahead of print]

80. Reddehase MJ (2002) Antigens and immunoevasins: opponents in cytomegalovirus immune surveillance. Nat Rev Immunol 2: 831–844. 12415307

81. Powers C, DeFilippis V, Malouli D, Fruh K (2008) Cytomegalovirus immune evasion. Curr Top Microbiol Immunol 325: 333–359. 18637515

82. Lemmermann NA, Gergely K, Böhm V, Deegen P, Daubner T, Reddehase MJ (2010) Immune evasion proteins of murine cytomegalovirus preferentially affect cell surface display of recently generated peptide presentation complexes. J Virol 84: 1221–1236. doi: 10.1128/JVI.02087-09 19906905

83. Jackson SE, Mason GM, Wills MR (2011) Human cytomegalovirus immunity and immune evasion. Virus Res 157: 151–160. doi: 10.1016/j.virusres.2010.10.031 21056604

84. Lemmermann NA, Böhm V, Holtappels R, Reddehase MJ (2011) In vivo impact of cytomegalovirus evasion of CD8 T-cell immunity: facts and thoughts based on murine models. Virus Res 157: 161–174. doi: 10.1016/j.virusres.2010.09.022 20933556

85. Holtappels R, Grzimek, Natascha K A, Simon CO, Thomas D, Dreis D, Reddehase MJ (2002) Processing and presentation of murine cytomegalovirus pORFm164-derived peptide in fibroblasts in the face of all viral immunosubversive early gene functions. J Virol 76: 6044–6053. 12021337

86. Holtappels R, Thomas D, Reddehase MJ (2009) The efficacy of antigen processing is critical for protection against cytomegalovirus disease in the presence of viral immune evasion proteins. J Virol 83: 9611–9615. doi: 10.1128/JVI.00936-09 19553308

87. Walter EA, Greenberg PD, Gilbert MJ, Finch RJ, Watanabe KS, Thomas ED et al. (1995) 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 333: 1038–1044. 7675046

88. Micklethwaite K, Hansen A, Foster A, Snape E, Antonenas V, Sartor M et al. (2007) Ex vivo expansion and prophylactic infusion of CMV-pp65 peptide-specific cytotoxic T-lymphocytes following allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 13: 707–714. 17531781

89. Meij P, Jedema I, Zandvliet ML, van der Heiden, Pim L J, van de Meent, Marian, van Egmond, Esther H M et al. (2012) Effective treatment of refractory CMV reactivation after allogeneic stem cell transplantation with in vitro-generated CMV pp65-specific CD8+ T-cell lines. J Immunother 35: 621–628. 22996368

90. Aubert G, Hassan-Walker AF, Madrigal JA, Emery VC, Morte C, Grace S et al. (2001) Cytomegalovirus-specific cellular immune responses and viremia in recipients of allogeneic stem cell transplants. J Infect Dis 184: 955–963. 11574909

91. Einsele H, Roosnek E, Rufer N, Sinzger C, Riegler S, Loffler J et al. (2002) Infusion of cytomegalovirus (CMV)-specific T cells for the treatment of CMV infection not responding to antiviral chemotherapy. Blood 99: 3916–3922. 12010789

92. Tu W, Chen S, Sharp M, Dekker C, Manganello AM, Tongson EC et al. (2004) Persistent and selective deficiency of CD4+ T cell immunity to cytomegalovirus in immunocompetent young children. J Immunol 172: 3260–3267. 14978134

93. Peggs KS, Thomson K, Samuel E, Dyer G, Armoogum J, Chakraverty R et al. (2011) Directly selected cytomegalovirus-reactive donor T cells confer rapid and safe systemic reconstitution of virus-specific immunity following stem cell transplantation. Clin Infect Dis 52: 49–57. doi: 10.1093/cid/ciq042 21148519

94. Reddehase MJ, Balthesen M, Rapp M, Jonjic S, Pavic I, Koszinowski UH (1994) The conditions of primary infection define the load of latent viral genome in organs and the risk of recurrent cytomegalovirus disease. J Exp Med 179: 185–193. 8270864

95. Kurz SK, Reddehase MJ (1999) Patchwork pattern of transcriptional reactivation in the lungs indicates sequential checkpoints in the transition from murine cytomegalovirus latency to recurrence. J Virol 73: 8612–8622. 10482614

96. Marquardt A, Halle S, Seckert CK, Lemmermann NA, Veres TZ, Braun A et al. (2011) Single cell detection of latent cytomegalovirus reactivation in host tissue. J Gen Virol 92: 1279–1291. doi: 10.1099/vir.0.029827-0 21325477

97. Seckert CK, Renzaho A, Tervo H, Krause C, Deegen P, Kuhnapfel B et al. (2009) Liver sinusoidal endothelial cells are a site of murine cytomegalovirus latency and reactivation. J Virol 83: 8869–8884. doi: 10.1128/JVI.00870-09 19535440

98. Seo S, Boeckh M (2013) Clinical Cytomegalovirus Research: Haematopoietic Cell Transplantation. In: Reddehase MJ, ed. Cytomegalovirus: From Molecular Pathogenesis to Intervention. Vol 2. Norfolk, UK: Caister Academic Press. pp. 337–353.

99. Plotkin S (2015) The history of vaccination against cytomegalovirus. Med Microbiol Immunol. 2015 Mar 20. [Epub ahead of print]

100. Wang X, Berger C, Wong CW, Forman SJ, Riddell SR, Jensen MC (2011) Engraftment of human central memory-derived effector CD8+ T cells in immunodeficient mice. Blood 117: 1888–1898. doi: 10.1182/blood-2010-10-310599 21123821

101. Gattinoni L, Lugli E, Ji Y, Pos Z, Paulos CM, Quigley MF et al. (2011) A human memory T cell subset with stem cell-like properties. Nat Med 17: 1290–1297. doi: 10.1038/nm.2446 21926977

102. Strowig T, Gurer C, Ploss A, Liu Y, Arrey F, Sashihara J et al. (2009) Priming of protective T cell responses against virus-induced tumors in mice with human immune system components. J Exp Med 206: 1423–1434. doi: 10.1084/jem.20081720 19487422

103. Thomas S, Klobuch S, Sommer M, van Ewijk R, Theobald M, Meyer RG et al. (2014) Human CD8+ memory and EBV-specific T cells show low alloreactivity in vitro and in CD34+ stem cell-engrafted NOD/SCID/IL-2Rgammac null mice. Exp Hematol 42: 28–38.e1–2. doi: 10.1016/j.exphem.2013.09.013 24120693

104. Podlech J, Holtappels R, Grzimek NK, Reddehase MJ (2002) Animal models: murine cytomegalovirus. In: Kaufmann SHE and Kabelitz D, eds. Methods in microbiology: immunology of infection. Vol. 32. Oxford, UK: Academic Press. pp. 493–525.

105. Bubic I, Wagner M, Krmpotic A, Saulig T, Kim S, Yokoyama WM et al. (2004) Gain of virulence caused by loss of a gene in murine cytomegalovirus. J Virol 78: 7536–7544. 15220428

106. Wagner M, Jonjic S, Koszinowski UH, Messerle M (1999) Systematic excision of vector sequences from the BAC-cloned herpesvirus genome during virus reconstitution. J Virol 73: 7056–7060. 10400809

107. Lemmermann NA, Podlech J, Seckert CK, Kropp KA, Grzimek NK, et al. (2010) CD8 T-Cell immunotherapy of cytomegalovirus disease in the murine model. In: Kaufmann SHE and Kabelitz D, eds. Methods in microbiology: immunology of infection. 2nd ed, Vol. 37. Oxford, UK: Academic Press. pp. 369–429.

108. Datsenko KA, Wanner BL (2000) One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci USA 97: 6640–6645. 10829079

109. Wehler TC, Nonn M, Brandt B, Britten CM, Grone M, Todorova M et al. (2007) Targeting the activation-induced antigen CD137 can selectively deplete alloreactive T cells from antileukemic and antitumor donor T-cell lines. Blood 109: 365–373. 16931626

110. Dörrschuck A, Schmidt A, Schnurer E, Gluckmann M, Albrecht C, Wolfel C et al. (2004) CD8+ cytotoxic T lymphocytes isolated from allogeneic healthy donors recognize HLA class Ia/Ib-associated renal carcinoma antigens with ubiquitous or restricted tissue expression. Blood 104: 2591–2599. 15231579

111. Heemskerk MH, Hagedoorn RS, van der Hoorn MA, van der Veken LT, Hoogeboom M, Kester MG et al. (2007) Efficiency of T-cell receptor expression in dual-specific T cells is controlled by the intrinsic qualities of the TCR chains within the TCR-CD3 complex. Blood 109: 235–243. 16968899

112. Szymczak AL, Workman CJ, Wang Y, Vignali KM, Dilioglou S, Vanin EF et al. (2004) Correction of multi-gene deficiency in vivo using a single 'self-cleaving' 2A peptide-based retroviral vector. Nat Biotechnol 22: 589–594. 15064769

113. Voss RH, Thomas S, Pfirschke C, Hauptrock B, Klobuch S, Kuball J et al. (2010) Coexpression of the T-cell receptor constant alpha domain triggers tumor reactivity of single-chain TCR-transduced human T cells. Blood 115: 5154–5163. doi: 10.1182/blood-2009-11-254078 20378753

114. Cicin-Sain L, Ruzsics Z, Podlech J, Bubic I, Menard C, Jonjic S et al. (2008) Dominant-negative FADD rescues the in vivo fitness of a cytomegalovirus lacking an antiapoptotic viral gene. J Virol 82: 2056–2064. 18094168

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2015 Číslo 7
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#