Table of Contents Author Guidelines Submit a Manuscript
Journal of Immunology Research
Volume 2016 (2016), Article ID 9384813, 8 pages
http://dx.doi.org/10.1155/2016/9384813
Review Article

Evaluation of T Cell Immunity against Human Cytomegalovirus: Impact on Patient Management and Risk Assessment of Vertical Transmission

Retrovirus Center, Department of Translational Research, University of Pisa, Via del Brennero 2, 56127 Pisa, Italy

Received 13 July 2016; Revised 7 October 2016; Accepted 17 October 2016

Academic Editor: Roberta A. Diotti

Copyright © 2016 Giulia Freer et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. S. Manicklal, V. C. Emery, T. Lazzarotto, S. B. Boppana, and R. K. Gupta, “The ‘silent’ global burden of congenital cytomegalovirus,” Clinical Microbiology Reviews, vol. 26, no. 1, pp. 86–102, 2013. View at Publisher · View at Google Scholar · View at Scopus
  2. E. J. Plosa, J. C. Esbenshade, M. P. Fuller, and J.-H. Weitkamp, “Cytomegalovirus infection,” Pediatrics in Review, vol. 33, no. 4, pp. 156–163, 2012. View at Publisher · View at Google Scholar · View at Scopus
  3. S. A. Ross, Z. Novak, S. Pati, and S. B. Boppana, “Overview of the diagnosis of cytomegalovirus infection,” Infectious Disorders—Drug Targets, vol. 11, no. 5, pp. 466–474, 2011. View at Publisher · View at Google Scholar · View at Scopus
  4. M. J. Revilleza, R. Wang, J. Mans, M. Hong, K. Natarajan, and D. H. Margulies, “How the virus outsmarts the host: function and structure of cytomegalovirus MHC-I-like molecules in the evasion of natural killer cell surveillance,” Journal of Biomedicine and Biotechnology, vol. 2011, Article ID 724607, 12 pages, 2011. View at Publisher · View at Google Scholar
  5. P. Engel and A. Angulo, “Viral immunomodulatory proteins: usurping host genes as a survival strategy,” Advances in Experimental Medicine and Biology, vol. 738, pp. 256–276, 2012. View at Publisher · View at Google Scholar · View at Scopus
  6. M. R. Wills, E. Poole, B. Lau, B. Krishna, and J. H. Sinclair, “The immunology of human cytomegalovirus latency: could latent infection be cleared by novel immunotherapeutic strategies?” Cellular and Molecular Immunology, vol. 12, no. 2, pp. 128–138, 2015. View at Publisher · View at Google Scholar · View at Scopus
  7. K. L. Springer and A. Weinberg, “Cytomegalovirus infection in the era of HAART: fewer reactivations and more immunity,” Journal of Antimicrobial Chemotherapy, vol. 54, no. 3, pp. 582–586, 2004. View at Publisher · View at Google Scholar · View at Scopus
  8. F. Zanghellini, S. B. Boppana, V. C. Emery, P. D. Griffiths, and R. F. Pass, “Asymptomatic primary cytomegalovirus infection: virologic and immunologic features,” Journal of Infectious Diseases, vol. 180, no. 3, pp. 702–707, 1999. View at Publisher · View at Google Scholar · View at Scopus
  9. D. Lilleri, C. Fornara, M. G. Revello, and G. Gerna, “Human cytomegalovirus-specific memory CD8+ and CD4+ T cell differentiation after primary infection,” The Journal of Infectious Diseases, vol. 15198, pp. 536–543, 2008. View at Google Scholar
  10. Z. W. Naing, G. M. Scott, A. Shand et al., “Congenital cytomegalovirus infection in pregnancy: a review of prevalence, clinical features, diagnosis and prevention,” Australian and New Zealand Journal of Obstetrics and Gynaecology, vol. 56, no. 1, pp. 9–18, 2016. View at Publisher · View at Google Scholar · View at Scopus
  11. I. Foulon, A. Naessens, W. Foulon, A. Casteels, and F. Gordts, “A 10-year prospective study of sensorineural hearing loss in children with congenital cytomegalovirus infection,” Journal of Pediatrics, vol. 153, no. 1, pp. 84–88, 2008. View at Publisher · View at Google Scholar · View at Scopus
  12. S. B. Boppana, L. B. Rivera, K. B. Fowler, M. Mach, and W. J. Britt, “Intrauterine transmission of cytomegalovirus to infants of women with preconceptional immunity,” The New England Journal of Medicine, vol. 344, no. 18, pp. 1366–1371, 2001. View at Publisher · View at Google Scholar · View at Scopus
  13. A. Kenneson and M. J. Cannon, “Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection,” Reviews in Medical Virology, vol. 17, no. 4, pp. 253–276, 2007. View at Publisher · View at Google Scholar · View at Scopus
  14. J. J. C. De Vries, E. W. van Zwet, F. W. Dekker, A. C. M. Kroes, P. H. Verkerk, and A. C. T. M. Vossen, “The apparent paradox of maternal seropositivity as a risk factor for congenital cytomegalovirus infection: a population-based prediction model,” Reviews in Medical Virology, vol. 23, no. 4, pp. 241–249, 2013. View at Publisher · View at Google Scholar · View at Scopus
  15. A. Roman, N. Manito, J. M. Campistol et al., “The impact of the prevention strategies on the indirect effects of CMV infection in solid organ transplant recipients,” Transplantation Reviews, vol. 28, no. 2, pp. 84–91, 2014. View at Publisher · View at Google Scholar · View at Scopus
  16. M. Pedersen and A. Seetharam, “Infections after orthotopic liver transplantation,” Journal of Clinical and Experimental Hepatology, vol. 4, no. 4, pp. 347–360, 2014. View at Publisher · View at Google Scholar · View at Scopus
  17. C. N. Kotton, D. Kumar, A. M. Caliendo et al., “Updated international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation,” Transplantation, vol. 96, no. 4, pp. 333–360, 2013. View at Publisher · View at Google Scholar · View at Scopus
  18. W. L. Drew, E. S. Sweet, R. C. Miner, and E. S. Mocarski, “Multiple infections by cytomegalovirus in patients with acquired immunodeficiency syndrome: documentation by Southern blot hybridization,” Journal of Infectious Diseases, vol. 150, no. 6, pp. 952–953, 1984. View at Publisher · View at Google Scholar · View at Scopus
  19. V. Aramă, R. Mihăilescu, M. Rădulescu et al., “Clinical relevance of the plasma load of cytomegalovirus in patients infected with HIV—a survival analysis,” Journal of Medical Virology, vol. 86, no. 11, pp. 1821–1827, 2014. View at Publisher · View at Google Scholar · View at Scopus
  20. N. Stern-Ginossar, B. Weisburd, A. Michalski et al., “Decoding human cytomegalovirus,” Science, vol. 338, no. 6110, pp. 1088–1093, 2012. View at Publisher · View at Google Scholar · View at Scopus
  21. K. Schoppel, B. Kropff, C. Schmidt, R. Vornhagen, and M. Mach, “The humoral immune response against human cytomegalovirus is characterized by a delayed synthesis of glycoprotein-specific antibodies,” Journal of Infectious Diseases, vol. 175, no. 3, pp. 533–544, 1997. View at Publisher · View at Google Scholar · View at Scopus
  22. A. Macagno, N. L. Bernasconi, F. Vanzetta et al., “Isolation of human monoclonal antibodies that potently neutralize human cytomegalovirus infection by targeting different epitopes on the gH/gL/UL128-131A complex,” Journal of Virology, vol. 84, no. 2, pp. 1005–1013, 2010. View at Publisher · View at Google Scholar · View at Scopus
  23. A. Huygens, N. Dauby, D. Vermijlen, and A. Marchant, “Immunity to cytomegalovirus in early life,” Frontiers in Immunology, vol. 5, article 552, 2014. View at Publisher · View at Google Scholar · View at Scopus
  24. M. Ohlin and C. Söderberg-Nauclér, “Human antibody technology and the development of antibodies against cytomegalovirus,” Molecular Immunology, vol. 67, no. 2, pp. 153–170, 2015. View at Publisher · View at Google Scholar · View at Scopus
  25. M. G. Revello, T. Lazzarotto, B. Guerra et al., “A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus,” The New England Journal of Medicine, vol. 370, no. 14, pp. 1316–1326, 2014. View at Publisher · View at Google Scholar · View at Scopus
  26. D. Lilleri, G. Gerna, M. Furione, M. Zavattoni, and A. Spinillo, “Neutralizing and ELISA IgG antibodies to human cytomegalovirus glycoprotein complexes may help date the onset of primary infection in pregnancy,” Journal of Clinical Virology, vol. 81, pp. 16–24, 2016. View at Publisher · View at Google Scholar
  27. D. Lilleri, A. Kabanova, M. G. Revello et al., “Fetal human cytomegalovirus transmission correlates with delayed maternal antibodies to gH/gL/pUL128-130-131 complex during primary infection,” PLoS ONE, vol. 8, no. 3, Article ID e59863, 2013. View at Publisher · View at Google Scholar · View at Scopus
  28. K. M. Bialas, T. Tanaka, D. Tran et al., “Maternal CD4+ T cells protect against severe congenital cytomegalovirus disease in a novel nonhuman primate model of placental cytomegalovirus transmission,” Proceedings of the National Academy of Sciences of the United States of America, vol. 112, no. 44, pp. 13645–13650, 2015. View at Publisher · View at Google Scholar · View at Scopus
  29. N. Terrazzini and F. Kern, “Cell-mediated immunity to human CMV infection: a brief overview,” F1000Prime Reports, vol. 6, article 28, 2014. View at Publisher · View at Google Scholar · View at Scopus
  30. A. W. Sylwester, B. L. Mitchell, J. B. Edgar et al., “Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects,” Journal of Experimental Medicine, vol. 202, no. 5, pp. 673–685, 2005. View at Publisher · View at Google Scholar · View at Scopus
  31. T. Bunde, A. Kirchner, B. Hoffmeister et al., “Protection from cytomegalovirus after transplantation is correlated with immediate early 1-specific CD8 T cells,” Journal of Experimental Medicine, vol. 201, no. 7, pp. 1031–1036, 2005. View at Publisher · View at Google Scholar · View at Scopus
  32. D. Melendez and R. R. Razonable, “Immune-based monitoring for cytomegalovirus infection in solid organ transplantation: is it ready for clinical primetime?” Expert Review of Clinical Immunology, vol. 10, no. 9, pp. 1213–1227, 2014. View at Publisher · View at Google Scholar · View at Scopus
  33. E. Blyth, L. Clancy, R. Simms et al., “Donor-derived CMV-specific T cells reduce the requirement for CMV-directed pharmacotherapy after allogeneic stem cell transplantation,” Blood, vol. 121, no. 18, pp. 3745–3758, 2013. View at Publisher · View at Google Scholar · View at Scopus
  34. G. Brestrich, S. Zwinger, A. Fischer et al., “Adoptive T-cell therapy of a lung transplanted patient with severe CMV disease and resistance to antiviral therapy,” American Journal of Transplantation, vol. 9, no. 7, pp. 1679–1684, 2009. View at Publisher · View at Google Scholar · View at Scopus
  35. C. Fornara, M. Furione, A. Arossa, G. Gerna, and D. Lilleri, “Comparative magnitude and kinetics of human cytomegalovirus-specific CD4+ and CD8+ T-cell responses in pregnant women with primary versus remote infection and in transmitting versus non-transmitting mothers: its utility for dating primary infection in pregnancy,” Journal of Medical Virology, vol. 88, no. 7, pp. 1238–1246, 2016. View at Publisher · View at Google Scholar · View at Scopus
  36. P. Klenerman and P. R. Dunbar, “CMV and the art of memory maintenance,” Immunity, vol. 17, no. 29, pp. 520–522, 2008. View at Google Scholar
  37. B. Pourgheysari, N. Khan, D. Best, R. Bruton, L. Nayak, and P. A. Moss, “The cytomegalovirus-specific CD4+ T-cell response expands with age and markedly alters the CD4+ T-cell repertoire,” Journal of Virology, vol. 8, pp. 7759–7765, 2007. View at Google Scholar
  38. D. Vermijlen, M. Brouwer, C. Donner et al., “Human cytomegalovirus elicits fetal γδ T cell responses in utero,” The Journal of Experimental Medicine, vol. 207, no. 4, pp. 807–821, 2010. View at Publisher · View at Google Scholar · View at Scopus
  39. V. Pitard, D. Roumanes, X. Lafarge et al., “Long-term expansion of effector/memory Vδ2γδT cells is a specific blood signature of CMV infection,” Blood, vol. 112, no. 4, pp. 1317–1324, 2008. View at Publisher · View at Google Scholar · View at Scopus
  40. T. E. O'Sullivan, J. C. Sun, and L. L. Lanier, “Natural killer cell memory,” Immunity, vol. 43, no. 4, pp. 634–645, 2015. View at Publisher · View at Google Scholar · View at Scopus
  41. A. Rölle, J. Pollmann, E.-M. Ewen et al., “IL-12-producing monocytes and HLA-E control HCMV-driven NKG2C+ NK cell expansion,” The Journal of Clinical Investigation, vol. 124, no. 12, pp. 5305–5316, 2014. View at Publisher · View at Google Scholar · View at Scopus
  42. G. W. G. Wilkinson, P. Tomasec, R. J. Stanton et al., “Modulation of natural killer cells by human cytomegalovirus,” Journal of Clinical Virology, vol. 41, no. 3, pp. 206–212, 2008. View at Publisher · View at Google Scholar · View at Scopus
  43. H. E. Prince and M. Lapé-Nixon, “Role of cytomegalovirus (CMV) IgG avidity testing in diagnosing primary CMV infection during pregnancy,” Clinical and Vaccine Immunology, vol. 21, no. 10, pp. 1377–1384, 2014. View at Publisher · View at Google Scholar · View at Scopus
  44. G. Forner, A. Saldan, C. Mengoli, N. Gussetti, G. Palù, and D. Abate, “CMV-ELISPOT but not CMV-QuantiFERON assay is a novel biomarker to determine the risk of congenital CMV infection in pregnant women,” Journal of Clinical Microbiology, vol. 54, no. 8, pp. 2149–2154, 2016. View at Publisher · View at Google Scholar
  45. Y. Eldar-Yedidia, M. Bar-Meir, M. Hillel et al., “Low interferon relative-response to cytomegalovirus is associated with low likelihood of intrauterine transmission of the virus,” PLoS ONE, vol. 11, no. 2, Article ID e0147883, 2016. View at Publisher · View at Google Scholar
  46. J. D. Stowell, K. Mask, M. Amin et al., “Cross-sectional study of cytomegalovirus shedding and immunological markers among seropositive children and their mothers,” BMC Infectious Diseases, vol. 14, article 568, 2014. View at Publisher · View at Google Scholar · View at Scopus
  47. R. H. Sedlak, L. Cook, A. Cheng, A. Magaret, and K. R. Jerome, “Clinical utility of droplet digital PCR for human cytomegalovirus,” Journal of Clinical Microbiology, vol. 52, no. 8, pp. 2844–2848, 2014. View at Publisher · View at Google Scholar · View at Scopus
  48. R. T. Hayden, Z. Gu, S. S. Sam et al., “Comparative performance of reagents and platforms for quantitation of cytomegalovirus DNA by digital PCR,” Journal of Clinical Microbiology, vol. 54, no. 10, pp. 2602–2608, 2016. View at Publisher · View at Google Scholar
  49. M. Ritter, T. Schmidt, J. Dirks et al., “Cytomegalovirus-specific T cells are detectable in early childhood and allow assignment of the infection status in children with passive maternal antibodies,” European Journal of Immunology, vol. 43, no. 4, pp. 1099–1108, 2013. View at Publisher · View at Google Scholar · View at Scopus
  50. T. Schmidt, D. Schub, M. Wolf et al., “Comparative analysis of assays for detection of cell-mediated immunity toward cytomegalovirus and M. tuberculosis in samples from deceased organ donors,” American Journal of Transplantation, vol. 14, no. 9, pp. 2159–2167, 2014. View at Publisher · View at Google Scholar · View at Scopus
  51. D. Lilleri, G. Gerna, M. Furione et al., “Use of a DNAemia cut-off for monitoring human cytomegalovirus infection reduces the number of preemptively treated children and young adults receiving hematopoietic stem-cell transplantation compared with qualitative pp65 antigenemia,” Blood, vol. 110, no. 7, pp. 2757–2760, 2007. View at Publisher · View at Google Scholar · View at Scopus
  52. M. Lúcia, E. Crespo, E. Melilli et al., “Preformed frequencies of cytomegalovirus (CMV)-specific memory T and B cells identify protected CMV-sensitized individuals among seronegative kidney transplant recipients,” Clinical Infectious Diseases, vol. 59, no. 11, pp. 1537–1545, 2014. View at Publisher · View at Google Scholar · View at Scopus
  53. J. D. Altman, P. A. Moss, P. J. Goulder, D. H. Barouch, M. G. McHeyzer-Williams, and J. I. Bell, “Phenotypic analysis of antigen-specific T lymphocytes,” Science, vol. 274, pp. 94–96, 1996. View at Google Scholar
  54. G. Freer, “Intracellular staining and detection of cytokines by fluorescence-activated flow cytometry,” Methods in Molecular Biology, vol. 1172, pp. 221–234, 2014. View at Publisher · View at Google Scholar · View at Scopus
  55. H. T. Maecker, J. Hassler, J. K. Payne et al., “Precision and linearity targets for validation of an IFNgamma ELISPOT, cytokine flow cytometry, and tetramer assay using CMV peptides,” BMC Immunology, vol. 9, article 9, 2008. View at Publisher · View at Google Scholar
  56. A. C. Hobeika, M. A. Morse, T. Osada et al., “Enumerating antigen-specific T-cell responses in peripheral blood: a comparison of peptide MHC Tetramer, ELISpot, and intracellular cytokine analysis,” Journal of Immunotherapy, vol. 28, pp. 63–72, 2005. View at Google Scholar
  57. J. W. Gratama, M. Boeckh, R. Nakamura et al., “Immune monitoring with iTAg MHC Tetramers for prediction of recurrent or persistent cytomegalovirus infection or disease in allogeneic hematopoietic stem cell transplant recipients: A Prospective Multicenter Study,” Blood, vol. 116, no. 10, pp. 1655–1662, 2010. View at Google Scholar
  58. S. Borchers, J. Ogonek, P. R. Varanasi et al., “Multimer monitoring of CMV-specific T cells in research and in clinical applications,” Diagnostic Microbiology and Infectious Disease, vol. 78, no. 3, pp. 201–212, 1953. View at Google Scholar
  59. D. Abate, M. Fiscon, A. Saldan et al., “Human cytomegalovirus-specific T-cell immune reconstitution in preemptively treated heart transplant recipients identifies subjects at critical risk for infection,” Journal of Clinical Microbiology, vol. 50, pp. 1974–1980, 2012. View at Google Scholar
  60. D. Abate, A. Saldan, C. Mengoli et al., “Comparison of cytomegalovirus (CMV) enzyme-linked immunosorbent spot and CMV quantiferon gamma interferon-releasing assays in assessing risk of CMV infection in kidney transplant recipients,” Journal of Clinical Microbiology, vol. 51, pp. 2501–2507, 2013. View at Google Scholar
  61. L. Nesher, D. P. Shah, E. J. Ariza-Heredia et al., “Utility of the enzyme-linked immunospot interferon-γ-release assay to predict the risk of cytomegalovirus infection in hematopoietic cell transplant recipients,” The Journal of Infectious Diseases, vol. 213, pp. 1701–1707, 2016. View at Google Scholar
  62. A. Saldan, G. Forner, C. Mengoli, N. Gussetti, G. Palù, and D. Abate, “Strong cell-mediated immune response to human cytomegalovirus is associated with increased risk of fetal infection in primarily infected pregnant women,” Clinical Infectious Diseases, vol. 61, pp. 1228–1234, 2015. View at Google Scholar
  63. A. C. Karlsson, J. N. Martin, S. R. Younger et al., “Comparison of the ELISPOT and cytokine flow cytometry assays for the enumeration of antigen-specific T cells,” Journal of Immunological Methods, vol. 283, no. 1-2, pp. 141–153, 2003. View at Publisher · View at Google Scholar · View at Scopus
  64. S. Walker, C. Fazou, T. Crough et al., “Ex vivo monitoring of human cytomegalovirus-specific CD8+ T-cell responses using QuantiFERON-CMV,” Transplant Infectious Disease, vol. 9, pp. 165–170, 2007. View at Google Scholar
  65. S. Tey -K, G. A. Kennedy, D. Cromer et al., “Clinical assessment of anti-viral CD8+ T cell immune monitoring using QuantiFERON-CMV® assay to identify high risk allogeneic hematopoietic stem cell transplant patients with CMV infection complications,” PloS One, vol. 8, article e74744, 2013. View at Google Scholar
  66. O. Manuel, S. Husain, D. Kumar et al., “Assessment of cytomegalovirus-specific cell-mediated immunity for the prediction of cytomegalovirus disease in high-risk solid-organ transplant recipients: a multicenter cohort study,” Clinical Infectious Diseases, vol. 56, pp. 817–824, 2013. View at Google Scholar
  67. A. Lochmanova, I. Lochman, H. Tomaskova et al., “Quantiferon-CMV test in prediction of cytomegalovirus infection after kidney transplantation,” Transplantation Proceedings, vol. 42, pp. 3574–3577, 2010. View at Google Scholar
  68. M. Á. Clari, B. Muñoz-Cobo, C. Solano et al., “Performance of the QuantiFERON-cytomegalovirus (CMV) assay for detection and estimation of the magnitude and functionality of the CMV-specific gamma interferon-producing CD8+ T-cell response in allogeneic stem cell transplant recipients,” Clinical and Vaccine Immunology, vol. 19, pp. 791–796, 2012. View at Google Scholar