T cell responses to cytomegalovirus

Nature Reviews Immunology

Volumn 16, Issue 6, 2016, Pages 367-377

  Klenerman, Paul ^a   Oxenius, Annette ^b  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b ETH ZURICH   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIGEN; CYTOKINE; T LYMPHOCYTE RECEPTOR;

AGING; ANTIGEN SPECIFICITY; CELL EXPANSION; CELL MATURATION; CYTOMEGALOVIRUS; CYTOMEGALOVIRUS INFECTION; HUMAN; LYMPHOCYTE FUNCTION; LYMPHOCYTE SUBPOPULATION; MEMORY T LYMPHOCYTE; NONHUMAN; PERSISTENT VIRUS INFECTION; PHENOTYPE; PRIORITY JOURNAL; REVIEW; T LYMPHOCYTE; VACCINATION; ANIMAL; GENETICS; HOST PATHOGEN INTERACTION; IMMUNOLOGICAL MEMORY; IMMUNOLOGY; METABOLISM; T LYMPHOCYTE SUBPOPULATION; VIROLOGY;

AGING; ANIMALS; CYTOMEGALOVIRUS; CYTOMEGALOVIRUS INFECTIONS; HOST-PATHOGEN INTERACTIONS; HUMANS; IMMUNOLOGIC MEMORY; T-CELL ANTIGEN RECEPTOR SPECIFICITY; T-LYMPHOCYTE SUBSETS; T-LYMPHOCYTES;

EID: 84964301308     PISSN: 14741733     EISSN: 14741741     Source Type: Journal    
DOI: 10.1038/nri.2016.38     Document Type: Review

References (145)

1. Borysiewicz L. K, et al. Human cytomegalovirus-specific cytotoxic T cells. Relative frequency of stage-specific CTL recognizing the 72 kD immediate early protein and glycoprotein B expressed by recombinant vaccinia viruses. J. Exp. Med. 168, 919-931 (1988).
2. Wills M. R, et al. 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 (1996).
3. Gillespie G. M, et al. Functional heterogeneity and high frequencies of cytomegalovirus-specific CD8+ T lymphocytes in healthy seropositive donors. J. Virol. 74, 8140-8150 (2000).
4. Sylwester A. W, et al. Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects. J. Exp. Med. 202, 673-685 (2005).
5. Jackson S. E, Mason G. M, Okecha G, Sissons J. G, & Wills M. R. Diverse specificities, phenotypes, and antiviral activities of cytomegalovirus-specific CD8+ T cells. J. Virol. 88, 10894-10908 (2014).
6. Komatsu H, et al. Large scale analysis of pediatric antiviral CD8+ T cell populations reveals sustained, functional and mature responses. Immun. Ageing. 3, 11 (2006).
7. Komatsu H, Sierro S, Cuero A. V, & Klenerman P. Population analysis of antiviral T cell responses using MHC class I peptide tetramers. Clin. Exp. Immunol. 134, 9-12 (2003).
8. Karrer U, et al. Memory inflation: continuous accumulation of antiviral CD8+ T cells over time. J. Immunol. 170, 2022-2029 (2003).
9. Holtappels R, Pahl-Seibert M. F, Thomas D, & Reddehase M. J. Enrichment of immediate-early 1 (m123/pp89) peptide-specific CD8 T cells in a pulmonary CD62Llo memory-effector cell pool during latent murine cytomegalovirus infection of the lungs. J. Virol. 74, 11495-11503 (2000).
10. Sylwester A, et al. A new perspective of the structural complexity of HCMV-specific T cell responses. Mech. Ageing Dev. http://dx.doi.org/10.1016/.j.mad.2016.03.002 (2016).
11. Khan N, Cobbold M, Keenan R, & Moss P. A. Comparative analysis of CD8+ T cell responses against human cytomegalovirus proteins pp65 and immediate early 1 shows similarities in precursor frequency, oligoclonality, and phenotype. J. Infect. Dis. 185, 1025-1034 (2002).
12. Ward S. M, et al. Virus-specific CD8+ T lymphocytes within the normal human liver. Eur. J. Immunol. 34, 1526-1531 (2004).
13. Akulian J. A, et al. High-quality CMV-specific CD4+ memory is enriched in the lung allograft and is associated with mucosal viral control. Am. J. Transplant. 13, 146-156 (2013).
14. Appay V, et al. Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections. Nat. Med. 8, 379-385 (2002).
15. Newell E. W, Sigal N, Bendall S. C, Nolan G. P, & Davis M. M. Cytometry by time of flight shows combinatorial cytokine expression and virus-specific cell niches within a continuum of CD8+ T cell phenotypes. Immunity. 36, 142-152 (2012).
16. Hertoghs K. M, et al. Molecular profiling of cytomegalovirus-induced human CD8+ T cell differentiation. J. Clin. Invest. 120, 4077-4090 (2010).
17. Boehme S. A, Lio F. M, Maciejewski-Lenoir D, Bacon K. B, & Conlon P. J. The chemokine fractalkine inhibits Fas-mediated cell death of brain microglia. J. Immunol. 165, 397-403 (2000).
18. Humphreys I. R, et al. Biphasic role of 4 1BB in the regulation of mouse cytomegalovirus-specific CD8+ T cells. Eur. J. Immunol. 40, 2762-2768 (2010).
19. Starck L, Scholz C, Dorken B, & Daniel P. T. Costimulation by CD137/4 1BB inhibits T cell apoptosis and induces Bcl xL and c FLIP(short) via phosphatidylinositol 3 kinase and AKT/protein kinase B. Eur. J. Immunol. 35, 1257-1266 (2005).
20. van Stijn A, et al. Human cytomegalovirus infection induces a rapid and sustained change in the expression of NK cell receptors on CD8+ T cells. J. Immunol. 180, 4550-4560 (2008).
21. Young N. T, & Uhrberg M. KIR expression shapes cytotoxic repertoires: a developmental program of survival. Trends Immunol. 23, 71-75 (2002).
22. Tchilian E. Z, & Beverley P. C. Altered CD45 expression and disease. Trends Immunol. 27, 146-153 (2006).
23. Lang A, & Nikolich-Zugich J. Functional CD8 T cell memory responding to persistent latent infection is maintained for life. J. Immunol. 187, 3759-3768 (2011).
24. Isa A, et al. Prolonged activation of virus-specific CD8+T cells after acute B19 infection. PLoS Med. 2, e343 (2005).
25. Simmons R, et al. Evolution of CD8+ T cell responses after acute PARV4 infection. J. Virol. 87, 3087-3096 (2013).
26. Bolinger B, et al. Adenoviral vector vaccination induces a conserved program of CD8+ T cell memory differentiation in mouse and man. Cell Rep. 13, 1578-1588 (2015).
27. Sallusto F, Lenig D, Forster R, Lipp M, & Lanzavecchia A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature. 401, 708-712 (1999).
28. Cui W, & Kaech S. M. Generation of effector CD8+ T cells and their conversion to memory T cells. Immunol. Rev. 236, 151-166 (2010).
29. Schenkel J. M, & Masopust D. Tissue-resident memory T cells. Immunity. 41, 886-897 (2014).
30. Thome J. J, & Farber D. L. Emerging concepts in tissue-resident T cells: lessons from humans. Trends Immunol. 36, 428-435 (2015).
31. Wherry E. J, & Kurachi M. Molecular and cellular insights into T cell exhaustion. Nat. Rev. Immunol. 15, 486-499 (2015).
32. Frebel H, Richter K, & Oxenius A. How chronic viral infections impact on antigen-specific T cell responses. Eur. J. Immunol. 40, 654-663 (2010).
33. Utzschneider D. T, et al. T cells maintain an exhausted phenotype after antigen withdrawal and population reexpansion. Nat. Immunol. 14, 603-610 (2013).
34. Shin H, Blackburn S. D, Blattman J. N, & Wherry E. J. Viral antigen and extensive division maintain virus-specific CD8 T cells during chronic infection. J. Exp. Med. 204, 941-949 (2007).
35. Blackburn S. D, et al. Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat. Immunol. 10, 29-37 (2009).
36. Seckert C. K, et al. Viral latency drives 'memory inflation': a unifying hypothesis linking two hallmarks of cytomegalovirus infection. Med. Microbiol. Immunol. 201, 551-566 (2012).
37. Liu X. F, et al. Epigenetic control of cytomegalovirus latency and reactivation. Viruses. 5, 1325-1345 (2013).
38. Torti N, & Oxenius A. T cell memory in the context of persistent herpes viral infections. Viruses 4 1116-1143 (2012).
39. Snyder C. M. Buffered memory: a hypothesis for the maintenance of functional, virus-specific CD8+ T cells during cytomegalovirus infection. Immunol. Res. 51, 195-204 (2011).
40. Snyder C. M, et al. Memory inflation during chronic viral infection is maintained by continuous production of short-lived, functional T cells. Immunity. 29, 650-659 (2008).
41. Torti N, Walton S. M, Brocker T, Rulicke T, & Oxenius A. Non-hematopoietic cells in lymph nodes drive memory CD8 T cell inflation during murine cytomegalovirus infection. PLoS Pathog. 7, e1002313 (2011).
42. Quinn M, et al. Memory T cells specific for murine cytomegalovirus re emerge after multiple challenges and recapitulate immunity in various adoptive transfer scenarios. J. Immunol. 194, 1726-1736 (2015).
43. Smith C. J, Turula H, & Snyder C. M. Systemic hematogenous maintenance of memory inflation by MCMV infection. PLoS Pathog. 10, e1004233 (2014).
44. Mekker A, et al. Immune senescence: relative contributions of age and cytomegalovirus infection. PLoS Pathog. 8, e1002850 (2012).
45. Loewendorf A. I, Arens R, Purton J. F, Surh C. D, & Benedict C. A. Dissecting the requirements for maintenance of the CMV-specific memory T cell pool. Viral Immunol. 24, 351-355 (2011).
46. Seckert C. K, et al. Antigen-presenting cells of haematopoietic origin prime cytomegalovirus-specific CD8 T cells but are not sufficient for driving memory inflation during viral latency. J. Gen. Virol. 92, 1994-2005 (2011).
47. Snyder C. M, Cho K. S, Bonnett E. L, Allan J. E, & Hill A. B. Sustained CD8+ T cell memory inflation after infection with a single-cycle cytomegalovirus. PLoS Pathog. 7, e1002295 (2011).
48. Redeker A, Welten S. P, & Arens R. Viral inoculum dose impacts memory T cell inflation. Eur. J. Immunol. 44, 1046-1057 (2014).
49. Beswick M, Pachnio A, Al Ali A, Sweet C, & Moss P. A. An attenuated temperature-sensitive strain of cytomegalovirus (tsm5) establishes immunity without development of CD8+ T cell memory inflation. J. Med. Virol. 85, 1968-1974 (2013).
50. Remmerswaal E. B, et al. Clonal evolution of CD8+ T cell responses against latent viruses: relationship among phenotype, localization, and function. J. Virol. 89, 568-580 (2015).
51. Pourgheysari B, et al. The cytomegalovirus-specific CD4+ T cell response expands with age and markedly alters the CD4+ T cell repertoire. J. Virol. 81, 7759-7765 (2007).
52. Arens R, et al. Cutting edge: murine cytomegalovirus induces a polyfunctional CD4 T cell response. J. Immunol. 180, 6472-6476 (2008).
53. Arens R, et al. Differential B7 CD28 costimulatory requirements for stable and inflationary mouse cytomegalovirus-specific memory CD8 T cell populations. J. Immunol. 186, 3874-3881 (2011).
54. Welten S. P, et al. CD27 CD70 costimulation controls T cell immunity during acute and persistent cytomegalovirus infection. J. Virol. 87, 6851-6865 (2013).
55. Welten S. P, et al. The viral context instructs the redundancy of costimulatory pathways in driving CD8+ T cell expansion. eLife 4 (2015).
56. Humphreys I. R, et al. OX40 costimulation promotes persistence of cytomegalovirus-specific CD8 T Cells: a CD4 dependent mechanism. J. Immunol. 179, 2195-2202 (2007).
57. Waller E. C, et al. Differential costimulation through CD137 (4 1BB) restores proliferation of human virus-specific effector memory (CD28- CD45RAHI) CD8+ T cells. Blood. 110, 4360-4366 (2007).
58. Malek T. R, & Castro I. Interleukin 2 receptor signaling: at the interface between tolerance and immunity. Immunity. 33, 153-165 (2010).
59. Bachmann M. F, Wolint P, Walton S, Schwarz K, & Oxenius A. Differential role of IL 2R signaling for CD8+ T cell responses in acute and chronic viral infections. Eur. J. Immunol. 37, 1502-1512 (2007).
60. Walton S. M, Torti N, Mandaric S, & Oxenius A. T cell help permits memory CD8+ T cell inflation during cytomegalovirus latency. Eur. J. Immunol. 41, 2248-2259 (2011).
61. Redeker A, et al. The quantity of autocrine IL 2 governs the expansion potential of CD8+ T cells. J. Immunol. 195, 4792-4801 (2015).
62. Frohlich A, et al. IL 21R on T cells is critical for sustained functionality and control of chronic viral infection. Science. 324, 1576-1580 (2009).
63. Yi J. S, Du M, & Zajac A. J. A vital role for interleukin 21 in the control of a chronic viral infection. Science 324 1572-1576 (2009).
64. Elsaesser H, Sauer K, & Brooks D. G. IL 21 is required to control chronic viral infection. Science. 324, 1569-1572 (2009).
65. Patterson J, Jesser R, & Weinberg A. Distinctive in vitro effects of T cell growth cytokines on cytomegalovirus-stimulated T cell responses of HIV-infected HAART recipients. Virology. 378, 48-57 (2008).
66. van Leeuwen E. M, et al. IL 7 receptor α chain expression distinguishes functional subsets of virus-specific human CD8+ T cells. Blood. 106, 2091-2098 (2005).
67. Munks M. W, et al. Four distinct patterns of memory CD8 T cell responses to chronic murine cytomegalovirus infection. J. Immunol. 177, 450-458 (2006).
68. Dekhtiarenko I, Jarvis M. A, Ruzsics Z, & Cicin- Sain L. The context of gene expression defines the immunodominance hierarchy of cytomegalovirus antigens. J. Immunol. 190, 3399-3409 (2013).
69. Grzimek N. K, Dreis D, Schmalz S, & Reddehase M. J. 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 (2001).
70. Munks M. W, et al. Genome-wide analysis reveals a highly diverse CD8 T cell response to murine cytomegalovirus. J. Immunol. 176, 3760-3766 (2006).
71. Torti N, Walton S. M, Murphy K. M, & Oxenius A. Batf3 transcription factor-dependent DC subsets in murine CMV infection: differential impact on T cell priming and memory inflation. Eur. J. Immunol. 41, 2612-2618 (2011).
72. Busche A, et al. Priming of CD8+ T cells against cytomegalovirus-encoded antigens is dominated by cross-presentation. J. Immunol. 190, 2767-2777 (2013).
73. Snyder C. M, Allan J. E, Bonnett E. L, Doom C. M, & Hill A. B. Cross-presentation of a spread-defective MCMV is sufficient to prime the majority of virus-specific CD8+ T cells. PLoS ONE 5, e9681 (2010).
74. Hutchinson S, et al. A dominant role for the immunoproteasome in CD8+ T cell responses to murine cytomegalovirus. PLoS ONE 6, e14646 (2011).
75. Van den Eynde B. J, & Morel S. Differential processing of class I restricted epitopes by the standard proteasome and the immunoproteasome. Curr. Opin. Immunol. 13, 147-153 (2001).
76. Farrington L. A, Smith T. A, Grey F, Hill A. B, & Snyder C. M. Competition for antigen at the level of the APC is a major determinant of immunodominance during memory inflation in murine cytomegalovirus infection. J. Immunol. 190, 3410-3416 (2013).
77. Turula H, Smith C. J, Grey F, Zurbach K. A, & Snyder C. M. Competition between T cells maintains clonal dominance during memory inflation induced by MCMV. Eur. J. Immunol. 43, 1252-1263 (2013).
78. Iancu E. M, et al. Clonotype selection and composition of human CD8 T cells specific for persistent herpes viruses varies with differentiation but is stable over time. J. Immunol. 183, 319-331 (2009).
79. Weekes M. P, Wills M. R, Mynard K, Carmichael A. J, & Sissons J. G. The memory cytotoxic T lymphocyte (CTL) response to human cytomegalovirus infection contains individual peptide-specific CTL clones that have undergone extensive expansion in vivo. J. Virol. 73, 2099-2108 (1999).
80. Schwanninger A, et al. Age-related appearance of a CMV-specific high-Avidity CD8+ T cell clonotype which does not occur in young adults. Immun. Ageing. 5, 14 (2008).
81. Miconnet I, et al. Large TCR diversity of virus-specific CD8 T cells provides the mechanistic basis for massive TCR renewal after antigen exposure. J. Immunol. 186, 7039-7049 (2011).
82. Wang G. C, Dash P, McCullers J. A, Doherty P. C, & Thomas P. G. T cell receptor αβ diversity inversely correlates with pathogen-specific antibody levels in human cytomegalovirus infection. Sci. Transl Med. 4, 128ra42 (2012).
83. Day E. K, et al. Rapid CD8+ T cell repertoire focusing and selection of high-Affinity clones into memory following primary infection with a persistent human virus: human cytomegalovirus. J. Immunol. 179, 3203-3213 (2007).
84. Trautmann L, et al. Selection of T cell clones expressing high-Affinity public TCRs within human cytomegalovirus-specific CD8 T cell responses. J. Immunol. 175, 6123-6132 (2005).
85. Griffiths S. J, et al. Age-Associated increase of low-Avidity cytomegalovirus-specific CD8+ T cells that re express CD45RA. J. Immunol. 190, 5363-5372 (2013).
86. Wynn K. K, et al. Impact of clonal competition for peptide-MHC complexes on the CD8+ T cell repertoire selection in a persistent viral infection. Blood. 111, 4283-4292 (2008).
87. Reddehase M. J, Mutter W, Munch K, Buhring H. J, & Koszinowski U. H. CD8 positive T lymphocytes specific for murine cytomegalovirus immediate-early antigens mediate protective immunity. J. Virol. 61, 3102-3108 (1987).
88. Alterio de Goss M, et al. 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 (1998).
89. Polic B, et al. Hierarchical and redundant lymphocyte subset control precludes cytomegalovirus replication during latent infection. J. Exp. Med. 188, 1047-1054 (1998).
90. Jonjic S, et al. Antibodies are not essential for the resolution of primary cytomegalovirus infection but limit dissemination of recurrent virus. J. Exp. Med. 179, 1713-1717 (1994).
91. 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. 64, 5457-5464 (1990).
92. Sumaria N, et al. The roles of interferon-gamma and perforin in antiviral immunity in mice that differ in genetically determined NK cell-mediated antiviral activity. Immunol. Cell Biol. 87, 559-566 (2009).
93. van Dommelen S. L, et al. Perforin and granzymes have distinct roles in defensive immunity and immunopathology. Immunity. 25, 835-848 (2006).
94. Lucin P, Pavic I, Polic B, Jonjic S, & Koszinowski U. H. interferon-dependent clearance of cytomegalovirus infection in salivary glands. J. Virol 66 1977-1984 (1992).
95. Jonjic S, Mutter W, Weiland F, Reddehase M. J, & Koszinowski U. H. Site-restricted persistent cytomegalovirus infection after selective long-Term depletion of CD4+ T lymphocytes. J. Exp. Med. 169, 1199-1212 (1989).
96. Walton S. M, et al. Absence of cross-presenting cells in the salivary gland and viral immune evasion confine cytomegalovirus immune control to effector CD4 T cells. PLoS Pathog. 7, e1002214 (2011).
97. Britt W. Manifestations of human cytomegalovirus infection: proposed mechanisms of acute and chronic disease. Curr. Top. Microbiol. Immunol. 325, 417-470 (2008).
98. Riddell S. R, et al. Restoration of viral immunity in immunodeficient humans by the adoptive transfer of T cell clones. Science. 257, 238-241 (1992).
99. Ebert S, et al. Parameters determining the efficacy of adoptive CD8 T cell therapy of cytomegalovirus infection. Med. Microbiol. Immunol. 201, 527-539 (2012).
100. Holtappels R, Bohm V, Podlech J, & Reddehase M. J. CD8 T cell-based immunotherapy of cytomegalovirus infection: proof of concept provided by the murine model. Med. Microbiol. Immunol. 197, 125-134 (2008).
101. Jeitziner S. M, Walton S. M, Torti N, & Oxenius A. Adoptive transfer of cytomegalovirus-specific effector CD4+ T cells provides antiviral protection from murine CMV infection. Eur. J. Immunol. 43, 2886-2895 (2013).
102. Walter E. A, et al. 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 (1995).
103. Gerna G, et al. Monitoring of human cytomegalovirus-specific CD4 and CD8 T cell immunity in patients receiving solid organ transplantation. Am. J. Transplant. 6, 2356-2364 (2006).
104. Einsele H, et al. Infusion of cytomegalovirus (CMV)- specific T cells for the treatment of CMV infection not responding to antiviral chemotherapy. Blood. 99, 3916-3922 (2002).
105. Fuji S, Kapp M, Grigoleit G. U, & Einsele H. Adoptive immunotherapy with virus-specific T cells. Best Pract. Res. Clin. Haematol. 24, 413-419 (2011).
106. Mui T. S, Kapp M, Einsele H, & Grigoleit G. U. T cell therapy for cytomegalovirus infection. Curr. Opin. Organ. Transplant. 15, 744-750 (2010).
107. Boeckh M, Murphy W. J, & Peggs K. S. Recent advances in cytomegalovirus: an update on pharmacologic and cellular therapies. Biol. Blood Marrow Transplant. 21, 24-29 (2015).
108. Simon C. O, et al. CD8 T cells control cytomegalovirus latency by epitope-specific sensing of transcriptional reactivation. J. Virol. 80, 10436-10456 (2006).
109. Bigley A. B, Spielmann G, Agha N, O'Connor D. P, & Simpson R. J. Dichotomous effects of latent CMV infection on the phenotype and functional properties of CD8+ T cells and NK cells. Cell. Immunol. 300, 26-32 (2015).
110. Steinert E. M, et al. Quantifying memory CD8 T cells reveals regionalization of immunosurveillance. Cell. 161, 737-749 (2015).
111. Turner D. L, et al. Lung niches for the generation and maintenance of tissue-resident memory T cells. Mucosal Immunol. 7, 501-510 (2014).
112. van Aalderen M. C, Remmerswaal E. B, ten Berge I. J, & van Lier R. A. Blood and beyond: properties of circulating and tissue-resident human virus-specific alphabeta CD8+ T cells. Eur. J. Immunol. 44, 934-944 (2014).
113. Thom J. T, Weber T. C, Walton S. M, Torti N, & Oxenius A. The salivary gland acts as a sink for tissue-resident memory CD8+ T cells, facilitating protection from local cytomegalovirus infection. Cell Rep. 13, 1125-1136 (2015).
114. Smith C. J, Caldeira-Dantas S, Turula H, & Snyder C. M. Murine CMV infection induces the continuous production of mucosal resident T cells. Cell Rep. 13, 1137-1148 (2015).
115. Lu X, Pinto A. K, Kelly A. M, Cho K. S, & Hill A. B. Murine cytomegalovirus interference with antigen presentation contributes to the inability of CD8 T cells to control virus in the salivary gland. J. Virol. 80, 4200-4202 (2006).
116. Holtappels R, et al. Subdominant CD8 T cell epitopes account for protection against cytomegalovirus independent of immunodomination. J. Virol. 82, 5781-5796 (2008).
117. Bohm V, et al. 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 (2008).
118. Nauerth M, et al. TCR-ligand koff rate correlates with the protective capacity of antigen-specific CD8+ T cells for adoptive transfer. Sci. Transl Med. 5, 192ra87 (2013).
119. Scheinberg P, et al. The transfer of adaptive immunity to CMV during hematopoietic stem cell transplantation is dependent on the specificity and phenotype of CMV-specific T cells in the donor. Blood. 114, 5071-5080 (2009).
120. Bunde T, et al. Protection from cytomegalovirus after transplantation is correlated with immediate early 1 specific CD8 T cells. J. Exp. Med. 201, 1031-1036 (2005).
121. Northfield J, Lucas M, Jones H, Young N. T, & Klenerman P. Does memory improve with age? CD85j (ILT 2/LIR 1) expression on CD8 T cells correlates with 'memory inflation' in human cytomegalovirus infection. Immunol. Cell Biol. 83, 182-188 (2005).
122. Khan N, et al. Herpesvirus-specific CD8 T cell immunity in old age: cytomegalovirus impairs the response to a coresident EBV infection. J. Immunol. 173, 7481-7489 (2004).
123. Stowe R. P, et al. Chronic herpesvirus reactivation occurs in aging. Exp. Gerontol. 42, 563-570 (2007).
124. Parry H. M, et al. Cytomegalovirus viral load within blood increases markedly in healthy people over the age of 70 years. Immun. Ageing. 13, 1 (2016).
125. Gkrania-Klotsas E, et al. Higher immunoglobulin G antibody levels against cytomegalovirus are associated with incident ischemic heart disease in the population-based EPIC-Norfolk cohort. J. Infect. Dis. 206, 1897-1903 (2012).
126. Roberts E. T, Haan M. N, Dowd J. B, & Aiello A. E. Cytomegalovirus antibody levels, inflammation, and mortality among elderly Latinos over 9 years of follow up. Am. J. Epidemiol. 172, 363-371 (2010).
127. Reunanen A, et al. Enterovirus, mycoplasma and other infections as predictors for myocardial infarction. J. Intern. Med. 252, 421-429 (2002).
128. Arai Y, et al. Inflammation, but not telomere length, predicts successful ageing at extreme old age: a longitudinal study of semi-supercentenarians. EBioMedicine. 2, 1549-1558 (2015).
129. van de Berg P. J, Yong S. L, Remmerswaal E. B, van Lier R. A, & ten Berge I. J. Cytomegalovirus-induced effector T cells cause endothelial cell damage. Clin. Vaccine Immunol. 19, 772-779 (2012).
130. Wikby A, et al. The immune risk phenotype is associated with IL 6 in the terminal decline stage: findings from the Swedish NONA immune longitudinal study of very late life functioning. Mech. Ageing Dev. 127, 695-704 (2006).
131. Strindhall J, et al. The inverted CD4/CD8 ratio and associated parameters in 66 year-old individuals: the Swedish HEXA immune study. Age (Dordr). 35, 985-991 (2013).
132. Spyridopoulos I, et al. CMV seropositivity and T cell senescence predict increased cardiovascular mortality in octogenarians: results from the Newcastle 85+ study. Aging Cell. 15, 389-392 (2015).
133. Briceno O, et al. Reduced naive CD8 T cell priming efficacy in elderly adults. Aging Cell. 15, 14-21 (2015).
134. McElhaney J. E, et al. Predictors of the antibody response to influenza vaccination in older adults with type 2 diabetes. BMJ Open Diabetes Res. Care 3, e000140 (2015).
135. O'Connor D, et al. The effect of chronic cytomegalovirus infection on pneumococcal vaccine responses. J. Infect. Dis. 209, 1635-1641 (2014).
136. Frasca D, Diaz A, Romero M, Landin A. M, & Blomberg B. B. Cytomegalovirus (CMV) seropositivity decreases B cell responses to the influenza vaccine. Vaccine. 33, 1433-1439 (2015).
137. Barton E. S, et al. Herpesvirus latency confers symbiotic protection from bacterial infection. Nature. 447, 326-329 (2007).
138. Yager E. J, et al. γ-Herpesvirus-induced protection against bacterial infection is transient. Viral Immunol 22 67-72 (2009).
139. Huygens A, Dauby N, Vermijlen D, & Marchant A. Immunity to cytomegalovirus in early life. Front. Immunol. 5, 552 (2014).
140. Murphy A. A, Redwood A. J, & Jarvis M. A. Self-disseminating vaccines for emerging infectious diseases. Expert Rev. Vaccines. 15, 31-39 (2016).
141. Karrer U, et al. Expansion of protective CD8+ T cell responses driven by recombinant cytomegaloviruses. J. Virol. 78, 2255-2264 (2004).
142. Hansen S. G, et al. Immune clearance of highly pathogenic SIV infection. Nature. 502, 100-104 (2013).
143. Hansen S. G, et al. Profound early control of highly pathogenic SIV by an effector memory T cell vaccine. Nature. 473, 523-527 (2011).
144. Hansen S. G, et al. Cytomegalovirus vectors violate CD8+ T cell epitope recognition paradigms. Science. 340, 1237874 (2013).
145. Bolinger B, et al. A new model for CD8+ T cell memory inflation based upon a recombinant adenoviral vector. J. Immunol 190 4162-4174 (2013).