Reduced Frequencies of Polyfunctional CMV-Specific T Cell Responses in Infants with Congenital CMV Infection

Journal of Clinical Immunology

Volumn 35, Issue 3, 2015, Pages 289-301

  Gibson, Laura ^a,g   Barysauskas, Constance M ^a,c   McManus, Margaret ^a   Dooley, Sheryl ^a,b   Lilleri, Daniele ^d   Fisher, Donna ^e   Srivastava, Tumul ^f   Diamond, Don J ^f   Luzuriaga, Katherine ^a  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^b Boston Heart Diagnostics   (United States)

^c DANA FARBER CANCER INSTITUTE   (United States)

^d FONDAZIONE IRCCS POLICLINICO SAN MATTEO   (Italy)

^e TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^f CITY OF HOPE NATIONAL MEDICAL CENTER   (United States)

^g UMASS MEMORIAL MEDICAL CENTER   (United States)

Author keywords

congenital; Cytomegalovirus; host immunity; neonate; polyfunction; T cells

Indexed keywords

CD45RA ANTIGEN; CHEMOKINE RECEPTOR CCR7; CYTOMEGALOVIRUS ANTIGEN PP65; GAMMA INTERFERON; IE 2 PEPTIDE; INTERLEUKIN 2; LYSOSOME ASSOCIATED MEMBRANE PROTEIN; MACROPHAGE INFLAMMATORY PROTEIN 1BETA; UNCLASSIFIED DRUG; VIRUS ANTIGEN; VIRUS DNA; VIRUS PROTEIN;

ADULT; ARTICLE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELLULAR IMMUNITY; CHRONICITY; CLINICAL ARTICLE; CONTROLLED STUDY; CYTOMEGALOVIRUS INFECTION; DISEASE DURATION; EFFECTOR CELL; FEMALE; FLOW CYTOMETRY; HUMAN; HUMAN CELL; INFANT; LYMPHOCYTE FUNCTION; MEMORY T LYMPHOCYTE; NEWBORN INFECTION; PERIPHERAL BLOOD MONONUCLEAR CELL; PHENOTYPE; PRIMARY INFECTION; PRIORITY JOURNAL; PROTEIN EXPRESSION; T LYMPHOCYTE SUBPOPULATION; VIRUS LOAD; BLOOD; CYTOMEGALOVIRUS; CYTOMEGALOVIRUS INFECTIONS; GENETICS; IMMUNOLOGY; NEWBORN;

ADULT; CD4-POSITIVE T-LYMPHOCYTES; CD8-POSITIVE T-LYMPHOCYTES; CYTOMEGALOVIRUS; CYTOMEGALOVIRUS INFECTIONS; DNA, VIRAL; HUMANS; INFANT; INFANT, NEWBORN;

EID: 84925503671     PISSN: 02719142     EISSN: 15732592     Source Type: Journal    
DOI: 10.1007/s10875-015-0139-3     Document Type: Article

References (76)

1. Stratton KR, Durch JS, Lawrence RS. Vaccines for the 21st Century: A Tool for Decisionmaking. Available at: http://www.nap.edu/catalog.php?record_id=5501. Stratton KR, Durch JS, Lawrence RS, editors. Washington, DC: National Academies Press; 2000.
2. Cannon MJ. Congenital cytomegalovirus (CMV) epidemiology and awareness. J Clin Virol. 2009;46 Suppl 4:S6–10.
3. Adler SP. Cytomegalovirus and child day care. Evidence for an increased infection rate among day-care workers. N Engl J Med. 1989;321(19):1290–6.
4. Adler SP. Cytomegalovirus and child day care: risk factors for maternal infection. Pediatr Infect Dis J. 1991;10(8):590–4.
5. Noyola DE, Demmler GJ, Williamson WD, Griesser C, Sellers S, Llorente A, et al. Cytomegalovirus urinary excretion and long term outcome in children with congenital cytomegalovirus infection. Congenital CMV Longitudinal Study Group. Pediatr Infect Dis J. 2000;19(6):505–10.
6. Krause PR, Bialek SR, Boppana SB, Griffiths PD, Laughlin CA, Ljungman P, et al. Priorities for CMV vaccine development. Vaccine. 2013.
7. Prendergast AJ, Klenerman P, Goulder PJ. The impact of differential antiviral immunity in children and adults. Nat Rev Immunol. 2012;12(9):636–48.
8. Lanzieri TM, Bialek SR, Ortega-Sanchez IR, Gambhir M. Modeling the potential impact of vaccination on the epidemiology of congenital cytomegalovirus infection. Vaccine. 2014.
9. Kharfan-Dabaja MA, Boeckh M, Wilck MB, Langston AA, Chu AH, Wloch MK, et al. A novel therapeutic cytomegalovirus DNA vaccine in allogeneic haemopoietic stem-cell transplantation: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Infect Dis. 2012;12(4):290–9.
10. Heineman TC, Schleiss M, Bernstein DI, Spaete RR, Yan L, Duke G, et al. A phase 1 study of 4 live, recombinant human cytomegalovirus Towne/Toledo chimeric vaccines. J Infect Dis. 2006;193(10):1350–60.
11. Schleiss MR. Cytomegalovirus in the neonate: immune correlates of infection and protection. Clin Dev Immunol. 2013;2013:501801.
12. Wussow F, Chiuppesi F, Martinez J, Campo J, Johnson E, Flechsig C, et al. Human cytomegalovirus vaccine based on the envelope gH/gL pentamer complex. PLoS Pathog. 2014;10(11):e1004524.
13. Zhong J, Khanna R. Delineating the role of CD4+ T cells in the activation of human cytomegalovirus-specific immune responses following immunization with Ad-gBCMVpoly vaccine: implications for vaccination of immunocompromised individuals. J Gen Virol. 2010;91(Pt 12):2994–3001.
14. Renzette N, Gibson L, Jensen JD, Kowalik TF. Human cytomegalovirus intrahost evolution-a new avenue for understanding and controlling herpesvirus infections. Curr Opin Virol. 2014;8:109–15.
15. La Rosa C, Diamond DJ. The immune response to human CMV. Futur Virol. 2012;7(3):279–93.
16. Bohm V, Podlech J, Thomas D, Deegen P, Pahl-Seibert MF, Lemmermann NA, et al. Epitope-specific in vivo protection against cytomegalovirus disease by CD8 T cells in the murine model of preemptive immunotherapy. Med Microbiol Immunol. 2008;197(2):135–44.
17. Jeitziner SM, Walton SM, Torti N, Oxenius A. Adoptive transfer of cytomegalovirus-specific effector CD4+ T cells provides antiviral protection from murine CMV infection. Eur J Immunol. 2013;43(11):2886–95.
18. Bunde T, Kirchner A, Hoffmeister B, Habedank D, Hetzer R, Cherepnev G, et al. Protection from cytomegalovirus after transplantation is correlated with immediate early 1-specific CD8 T cells. J Exp Med. 2005;201(7):1031–6.
19. Gamadia LE, Remmerswaal EB, Weel JF, Bemelman F, van Lier RA, Ten Berge IJ. Primary immune responses to human CMV: a critical role for IFN-gamma-producing CD4+ T cells in protection against CMV disease. Blood. 2003;101(7):2686–92.
20. Sacre K, Carcelain G, Cassoux N, Fillet AM, Costagliola D, Vittecoq D, et al. Repertoire, diversity, and differentiation of specific CD8 T cells are associated with immune protection against human cytomegalovirus disease. J Exp Med. 2005;201(12):1999–2010.
21. Luo XH, Huang XJ, Liu KY, Xu LP, Liu DH. Protective immunity transferred by infusion of cytomegalovirus-specific CD8(+) T cells within donor grafts: its associations with cytomegalovirus reactivation following unmanipulated allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2010;16(7):994–1004.
22. Chen SF, Tu WW, Sharp MA, Tongson EC, He XS, Greenberg HB, et al. Antiviral CD8 T cells in the control of primary human cytomegalovirus infection in early childhood. J Infect Dis. 2004;189(9):1619–27.
23. Gibson L, Dooley S, Trzmielina S, Somasundaran M, Fisher D, Revello MG, et al. Cytomegalovirus (CMV) IE1- and pp 65-specific CD8+ T cell responses broaden over time after primary CMV infection in infants. J Infect Dis. 2007;195(12):1789–98.
24. Gibson L, Piccinini G, Lilleri D, Revello MG, Wang Z, Markel S, et al. Human cytomegalovirus proteins pp 65 and immediate early protein 1 are common targets for CD8+ T cell responses in children with congenital or postnatal human cytomegalovirus infection. J Immunol. 2004;172(4):2256–64.
25. Marchant A, Appay V, Van Der Sande M, Dulphy N, Liesnard C, Kidd M, et al. Mature CD8(+) T lymphocyte response to viral infection during fetal life. J Clin Invest. 2003;111(11):1747–55.
26. Miles DJ, Sande M, Kaye S, Crozier S, Ojuola O, Palmero MS, et al. CD4(+) T cell responses to cytomegalovirus in early life: a prospective birth cohort study. J Infect Dis. 2008;197(5):658–62.
27. Tu W, Chen S, Sharp M, Dekker C, Manganello AM, Tongson EC, et al. Persistent and selective deficiency of CD4+ T cell immunity to cytomegalovirus in immunocompetent young children. J Immunol. 2004;172(5):3260–7.
28. Lidehall AK, Engman ML, Sund F, Malm G, Lewensohn-Fuchs I, Ewald U, et al. Cytomegalovirus-specific CD4 and CD8 T cell responses in infants and children. Scand J Immunol. 2013;77(2):135–43.
29. Mahnke YD, Brodie TM, Sallusto F, Roederer M, Lugli E. The who’s who of T-cell differentiation: human memory T-cell subsets. Eur J Immunol. 2013;43(11):2797–809.
30. Betts MR, Nason MC, West SM, De Rosa SC, Migueles SA, Abraham J, et al. HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood. 2006;107(12):4781–9.
31. Nebbia G, Mattes FM, Smith C, Hainsworth E, Kopycinski J, Burroughs A, et al. Polyfunctional cytomegalovirus-specific CD4+ and pp 65 CD8+ T cells protect against high-level replication after liver transplantation. Am J Transplant. 2008;8(12):2590–9.
32. Zhou W, Longmate J, Lacey SF, Palmer JM, Gallez-Hawkins G, Thao L, et al. Impact of donor CMV status on viral infection and reconstitution of multifunction CMV-specific T cells in CMV-positive transplant recipients. Blood. 2009;113(25):6465–76.
33. Bernstein DI, Reap EA, Katen K, Watson A, Smith K, Norberg P, et al. Randomized, double-blind, Phase 1 trial of an alphavirus replicon vaccine for cytomegalovirus in CMV seronegative adult volunteers. Vaccine. 2009;28(2):484–93.
34. Precopio ML, Betts MR, Parrino J, Price DA, Gostick E, Ambrozak DR, et al. Immunization with vaccinia virus induces polyfunctional and phenotypically distinctive CD8(+) T cell responses. J Exp Med. 2007;204(6):1405–16.
35. Soares AP, Scriba TJ, Joseph S, Harbacheuski R, Murray RA, Gelderbloem SJ, et al. Bacillus Calmette-Guerin vaccination of human newborns induces T cells with complex cytokine and phenotypic profiles. J Immunol. 2008;180(5):3569–77.
36. Schmueck M, Fischer AM, Hammoud B, Brestrich G, Fuehrer H, Luu SH, et al. Preferential expansion of human virus-specific multifunctional central memory T cells by partial targeting of the IL-2 receptor signaling pathway: the key role of CD4+ T cells. J Immunol. 2012;188(10):5189–98.
37. Gerna G, Revello MG, Percivalle E, Zavattoni M, Parea M, Battaglia M. Quantification of human cytomegalovirus viremia by using monoclonal antibodies to different viral proteins. J Clin Microbiol. 1990;28(12):2681–8.
38. Revello MG, Zavattoni M, Baldanti F, Sarasini A, Paolucci S, Gerna G. Diagnostic and prognostic value of human cytomegalovirus load and IgM antibody in blood of congenitally infected newborns. J Clin Virol. 1999;14(1):57–66.
39. Revello MG, Zavattoni M, Sarasini A, Percivalle E, Simoncini L, Gerna G. Human cytomegalovirus in blood of immunocompetent persons during primary infection: prognostic implications for pregnancy. J Infect Dis. 1998;177(5):1170–5.
40. Revello MG, Gerna G. Diagnosis and management of human cytomegalovirus infection in the mother, fetus, and newborn infant. Clin Microbiol Rev. 2002;15(4):680–715.
41. Revello MG, Lilleri D, Zavattoni M, Furione M, Genini E, Comolli G, et al. Lymphoproliferative response in primary human cytomegalovirus (HCMV) infection is delayed in HCMV transmitter mothers. J Infect Dis. 2006;193(2):269–76.
42. Jones CE, Naidoo S, De Beer C, Esser M, Kampmann B, Hesseling AC. Maternal HIV infection and antibody responses against vaccine-preventable diseases in uninfected infants. JAMA. 2011;305(6):576–84.
43. Johnson DC, McFarland EJ, Muresan P, Fenton T, McNamara J, Read JS, et al. Safety and immunogenicity of an HIV-1 recombinant canarypox vaccine in newborns and infants of HIV-1-infected women. J Infect Dis. 2005;192(12):2129–33.
44. Wang Z, Zhou W, Srivastava T, La Rosa C, Mandarino A, Forman SJ, et al. A fusion protein of HCMV IE1 exon4 and IE2 exon5 stimulates potent cellular immunity in an MVA vaccine vector. Virology. 2008;377(2):379–90.
45. Revello MG, Sarasini A, Zavattoni M, Baldanti F, Gerna G. Improved prenatal diagnosis of congenital human cytomegalovirus infection by a modified nested polymerase chain reaction. J Med Virol. 1998;56(1):99–103.
46. Gerna G, Vitulo P, Rovida F, Lilleri D, Pellegrini C, Oggionni T, et al. Impact of human metapneumovirus and human cytomegalovirus versus other respiratory viruses on the lower respiratory tract infections of lung transplant recipients. J Med Virol. 2006;78(3):408–16.
47. Roederer M, Nozzi JL, Nason MC. SPICE: exploration and analysis of post-cytometric complex multivariate datasets. Cytometry A. 2011;79(2):167–74.
48. Lazzarotto T, Guerra B, Lanari M, Gabrielli L, Landini MP. New advances in the diagnosis of congenital cytomegalovirus infection. J Clin Virol. 2008;41(3):192–7.
49. Sylwester AW, Mitchell BL, Edgar JB, Taormina C, Pelte C, Ruchti 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(5):673–85.
50. Griffiths P, Plotkin S, Mocarski E, Pass R, Schleiss M, Krause P, et al. Desirability and feasibility of a vaccine against cytomegalovirus. Vaccine. 2013;31 Suppl 2:B197–203.
51. Azevedo RS, Amaku M. Modelling immunization strategies with cytomegalovirus vaccine candidates. Epidemiol Infect. 2011;139(12):1818–26.
52. Mansoor N, Abel B, Scriba TJ, Hughes J, de Kock M, Tameris M, et al. Significantly skewed memory CD8+ T cell subsets in HIV-1 infected infants during the first year of life. Clin Immunol. 2009;130(3):280–9.
53. Schietinger A, Greenberg PD. Tolerance and exhaustion: defining mechanisms of T cell dysfunction. Trends Immunol. 2014;35(2):51–60.
54. Fulop T, Larbi A, Pawelec G. Human T cell aging and the impact of persistent viral infections. Front Immunol. 2013;4:271.
55. Bronke C, Jansen CA, Westerlaken GH, De Cuyper IM, Miedema F, Tesselaar K, et al. Shift of CMV-specific CD4+ T-cells to the highly differentiated CD45RO-CD27- phenotype parallels loss of proliferative capacity and precedes progression to HIV-related CMV end-organ disease. Clin Immunol. 2007;124(2):190–9.
56. Pourgheysari B, Piper KP, McLarnon A, Arrazi J, Bruton R, Clark F, et al. Early reconstitution of effector memory CD4+ CMV-specific T cells protects against CMV reactivation following allogeneic SCT. Bone Marrow Transplant. 2009;43(11):853–61.
57. Lilleri D, Fornara C, Revello MG, Gerna G. Human cytomegalovirus-specific memory CD8+ and CD4+ T cell differentiation after primary infection. J Infect Dis. 2008;198(4):536–43.
58. Casazza JP, Betts MR, Price DA, Precopio ML, Ruff LE, Brenchley JM, et al. Acquisition of direct antiviral effector functions by CMV-specific CD4+ T lymphocytes with cellular maturation. J Exp Med. 2006;203(13):2865–77.
59. Gehrz RC, Marker SC, Knorr SO, Kalis JM, Balfour Jr HH. Specific cell-mediated immune defect in active cytomegalovirus infection of young children and their mothers. Lancet. 1977;2(8043):844–7.
60. Pass RF, Stagno S, Britt WJ, Alford CA. Specific cell-mediated immunity and the natural history of congenital infection with cytomegalovirus. J Infect Dis. 1983;148(6):953–61.
61. Starr SE, Tolpin MD, Friedman HM, Paucker K, Plotkin SA. Impaired cellular immunity to cytomegalovirus in congenitally infected children and their mothers. J Infect Dis. 1979;140(4):500–5.
62. Pass RF, Dworsky ME, Whitley RJ, August AM, Stagno S, Alford Jr CA. Specific lymphocyte blastogenic responses in children with cytomegalovirus and herpes simplex virus infections acquired early in infancy. Infect Immun. 1981;34(1):166–70.
63. Kim TK, St John LS, Wieder ED, Khalili J, Ma Q, Komanduri KV. Human late memory CD8+ T cells have a distinct cytokine signature characterized by CC chemokine production without IL-2 production. J Immunol. 2009;183(10):6167–74.
64. Riou C, Treurnicht F, Abrahams MR, Mlisana K, Liu MK, Goonetilleke N, et al. Increased memory differentiation is associated with decreased polyfunctionality for HIV but not for cytomegalovirus-specific CD8+ T cells. J Immunol. 2012;189(8):3838–47.
65. Thobakgale CF, Streeck H, Mkhwanazi N, Mncube Z, Maphumulo L, Chonco F, et al. Short communication: CD8(+) T cell polyfunctionality profiles in progressive and nonprogressive pediatric HIV type 1 infection. AIDS Res Hum Retroviruses. 2011;27(9):1005–12.
66. Huang S, Dunkley-Thompson J, Tang Y, Macklin EA, Steel-Duncan J, Singh-Minott I, et al. Deficiency of HIV-Gag-specific T cells in early childhood correlates with poor viral containment. J Immunol. 2008;181(11):8103–11.
67. Ritz N, Strach M, Yau C, Dutta B, Tebruegge M, Connell TG, et al. A comparative analysis of polyfunctional T cells and secreted cytokines induced by Bacille Calmette-Guerin immunisation in children and adults. PLoS One. 2012;7(7):e37535.
68. Cannon MJ, Hyde TB, Schmid DS. Review of cytomegalovirus shedding in bodily fluids and relevance to congenital cytomegalovirus infection. Rev Med Virol. 2011;21(4):240–55.
69. Kimberlin DW, Lin CY, Sanchez PJ, Demmler GJ, Dankner W, Shelton M, et al. Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial. J Pediatr. 2003;143(1):16–25.
70. McCarron MJ, Reen DJ. Neonatal CD8+ T-cell differentiation is dependent on interleukin-12. Hum Immunol. 2010;71(12):1172–9.
71. Debock I, Flamand V. Unbalanced neonatal CD4(+) T-cell immunity. Front Immunol. 2014;5:393.
72. Sandberg JK, Fast NM, Jordan KA, Furlan SN, Barbour JD, Fennelly G, et al. HIV-specific CD8+ T cell function in children with vertically acquired HIV-1 infection is critically influenced by age and the state of the CD4+ T cell compartment. J Immunol. 2003;170(8):4403–10.
73. Antoine P, Olislagers V, Huygens A, Lecomte S, Liesnard C, Donner C, et al. Functional exhaustion of CD4+ T lymphocytes during primary cytomegalovirus infection. J Immunol. 2012;189(5):2665–72.
74. Slavuljica I, Kvestak D, Huszthy PC, Kosmac K, Britt WJ, Jonjic S. Immunobiology of congenital cytomegalovirus infection of the central nervous system-the murine cytomegalovirus model. Cell Mol Immunol. 2014.
75. Gabrielli L, Bonasoni MP, Santini D, Piccirilli G, Chiereghin A, Petrisli E, et al. Congenital cytomegalovirus infection: patterns of fetal brain damage. Clin Microbiol Infect. 2012;18(10):E419–27.
76. Khan N, Bruton R, Taylor GS, Cobbold M, Jones TR, Rickinson AB, et al. Identification of cytomegalovirus-specific cytotoxic T lymphocytes in vitro is greatly enhanced by the use of recombinant virus lacking the US2 to US11 region or modified vaccinia virus Ankara expressing individual viral genes. J Virol. 2005;79(5):2869–79.