Skip to main content

Advertisement

SpringerLink
Log in

A constant companion: immune recognition and response to cytomegalovirus with aging and implications for immune fitness

  • Conference Proceedings
  • Published:
GeroScience Aims and scope Submit manuscript

Abstract

Approximately 50% of individuals aged 6–49 years in the United States are infected with cytomegalovirus (CMV), with seroprevalence increasing with age, reaching 85–90% by 75–80 years according to Bate et al. (Clin Infect Dis 50 (11): 1439-1447, 2010) and Pawelec et al. (Curr Opin Immunol 24:507-511, 2012). Following primary infection, CMV establishes lifelong latency with periodic reactivation. Immunocompetent hosts experience largely asymptomatic infection, but CMV can cause serious illness in immunocompromised populations, such as transplant patients and the elderly. Control of CMV requires constant immune surveillance, and recent discoveries suggest this demand alters general features of the immune system in infected individuals. Here, we review recent advances in the understanding of the immune response to CMV and the role of CMV in immune aging and fitness, while highlighting the importance of potential confounding factors that influence CMV studies. Understanding how CMV contributes to shaping “baseline” immunity has important implications for a host’s ability to mount effective responses to diverse infections and vaccination.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Alejenef A, Pachnio A, Halawi M et al (2014) Cytomegalovirus drives Vδ2neg γδ T cell inflation in many healthy virus carriers with increasing age. Clin Exp Immunol 176:418–428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ančicová L, Wágnerová M, Janulíková J et al (2015) Simultaneous infection with gammaherpes and influenza viruses enhances the host immune defense. Acta Virol 59:369–379

    Article  PubMed  Google Scholar 

  • Bajwa M, Vita S, Vescovini R et al (2017) CMV-specific T-cell responses at older ages: broad responses with a large central memory component may be key to long-term survival. J Infect Dis 215:1212–1220

    Article  PubMed  Google Scholar 

  • Bartel Y, Bauer B, Steinle A (2013) Modulation of NK cell function by genetically coupled C-type lectin-like receptor/ligand pairs encoded in the human natural killer gene complex. Front Immunol 4:362

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Barton ES, White DW, Cathelyn JS et al (2007) Herpesvirus latency confers symbiotic protection from bacterial infection. Nature 447:326–329

    Article  CAS  PubMed  Google Scholar 

  • Bate SL, Dollard SC, Cannon MJ (2010) Cytomegalovirus seroprevalence in the United States: the national health and nutrition examination surveys, 1988–2004. Clin Infect Dis 50(11): 1439-1447

  • Bayard C, Lepetitcorps H, Roux A et al (2016) Coordinated expansion of both memory T cells and NK cells in response to CMV infection in humans. Eur J Immunol 46:1168–1179

    Article  CAS  PubMed  Google Scholar 

  • Bayram A, Ozkur A, Erkilic S (2009) Prevalence of human cytomegalovirus co-infection in patients with chronic viral hepatitis B and C: a comparison of clinical and histological aspects. J Clin Virol 45:212–217

    Article  PubMed  Google Scholar 

  • Betts MR, Nason MC, West SM et al (2006) HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood 107:4781–4789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Béziat V, Liu LL, Malmberg J-A et al (2013) NK cell responses to cytomegalovirus infection lead to stable imprints in the human KIR repertoire and involve activating KIRs. Blood 121:2678–2688

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Boehme KW, Guerrero M, Compton T (2006) Human cytomegalovirus envelope glycoproteins B and H are necessary for TLR2 activation in permissive cells. J Immunol 177:7094–7102

    Article  CAS  PubMed  Google Scholar 

  • Botto S, Streblow DN, DeFilippis V et al (2011) IL-6 in human cytomegalovirus secretome promotes angiogenesis and survival of endothelial cells through the stimulation of survivin. Blood 117:352–361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boyd A, Almeida JR, Darrah PA et al (2015) Pathogen-specific T cell polyfunctionality is a correlate of T cell efficacy and immune protection. PLoS One 10:e0128714

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Brodin P, Jojic V, Gao T et al (2015) Variation in the human immune system is largely driven by non-heritable influences. Cell 160:37–47

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brown MG, Dokun AO, Heusel JW et al (2001) Vital involvement of a natural killer cell activation receptor in resistance to viral infection. Science 292:934–937

    Article  CAS  PubMed  Google Scholar 

  • Bubić I, Wagner M, Krmpotić A et al (2004) Gain of virulence caused by loss of a gene in murine cytomegalovirus. J Virol 78:7536–7544

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Che JW, Daniels KA, Selin LK, Welsh RM (2017) Heterologous immunity and persistent murine cytomegalovirus infection. J Virol. doi:10.1128/JVI.01386-16

  • Chiu Y-L, Lin C-H, Sung B-Y et al (2016) Cytotoxic polyfunctionality maturation of cytomegalovirus-pp65-specific CD4 + and CD8 + T-cell responses in older adults positively correlates with response size. Sci Rep 6:19227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cicin-Sain L, Sylwester AW, Hagen SI et al (2011) Cytomegalovirus-specific T cell immunity is maintained in immunosenescent rhesus macaques. J Immunol 187:1722–1732

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Crough T, Khanna R (2009) Immunobiology of human cytomegalovirus: from bench to bedside. Clin Microbiol Rev 22:76–98 Table of contents

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Darrah PA, Patel DT, De Luca PM et al (2007) Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major. Nat Med 13:843–850

    Article  CAS  PubMed  Google Scholar 

  • DeFilippis VR, Alvarado D, Sali T et al (2010) Human cytomegalovirus induces the interferon response via the DNA sensor ZBP1. J Virol 84:585–598

    Article  CAS  PubMed  Google Scholar 

  • Derhovanessian E, Theeten H, Hähnel K et al (2013) Cytomegalovirus-associated accumulation of late-differentiated CD4 T-cells correlates with poor humoral response to influenza vaccination. Vaccine 31:685–690

    Article  CAS  PubMed  Google Scholar 

  • den Elzen WPJ, Vossen ACMT, Cools HJM et al (2011) Cytomegalovirus infection and responsiveness to influenza vaccination in elderly residents of long-term care facilities. Vaccine 29:4869–4874

    Article  CAS  Google Scholar 

  • Emerson RO, DeWitt WS, Vignali M et al (2017) Immunosequencing identifies signatures of cytomegalovirus exposure history and HLA-mediated effects on the T cell repertoire. Nat Genet 49:659–665

    Article  CAS  PubMed  Google Scholar 

  • Fletcher JM, Vukmanovic-Stejic M, Dunne PJ et al (2005) Cytomegalovirus-specific CD4+ T cells in healthy carriers are continuously driven to replicative exhaustion. J Immunol 175:8218–8225

    Article  CAS  PubMed  Google Scholar 

  • Freeman ML, Mudd JC, Shive CL et al (2016) CD8 T-cell expansion and inflammation linked to CMV coinfection in ART-treated HIV infection. Clin Infect Dis 62:392–396

    Article  PubMed  Google Scholar 

  • Furman D, Jojic V, Sharma S et al (2015) Cytomegalovirus infection enhances the immune response to influenza. Sci Transl Med 7:281ra43

    Article  PubMed  PubMed Central  Google Scholar 

  • Gariano GR, Dell’Oste V, Bronzini M et al (2012) The intracellular DNA sensor IFI16 gene acts as restriction factor for human cytomegalovirus replication. PLoS Pathog 8:e1002498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gazit R, Garty B-Z, Monselise Y et al (2004) Expression of KIR2DL1 on the entire NK cell population: a possible novel immunodeficiency syndrome. Blood 103:1965–1966

    Article  CAS  PubMed  Google Scholar 

  • Gianella S, Anderson CM, Var SR et al (2016) Replication of human herpesviruses is associated with higher HIV DNA levels during antiretroviral therapy started at early phases of HIV infection. J Virol 90:3944–3952

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gianella S, Anderson CM, Vargas MV et al (2013) Cytomegalovirus DNA in semen and blood is associated with higher levels of proviral HIV DNA. J Infect Dis 207:898–902

    Article  CAS  PubMed  Google Scholar 

  • Gianella S, Massanella M, Richman DD et al (2014) Cytomegalovirus replication in semen is associated with higher levels of proviral HIV DNA and CD4+ T cell activation during antiretroviral treatment. J Virol 88:7818–7827

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hadrup SR, Strindhall J, Køllgaard T et al (2006) Longitudinal studies of clonally expanded CD8 T cells reveal a repertoire shrinkage predicting mortality and an increased number of dysfunctional cytomegalovirus-specific T cells in the very elderly. J Immunol 176:2645–2653

    Article  CAS  PubMed  Google Scholar 

  • Holtappels R, Pahl-Seibert M-F, Thomas D, Reddehase MJ (2000) 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hraiech S, Bordes J, Mège JL et al (2017) Cytomegalovirus reactivation enhances the virulence of Staphylococcus aureus pneumonia in a mouse model. Clin Microbiol Infect 23:38–45

    Article  CAS  PubMed  Google Scholar 

  • Huang Y, Liu L, Ma D et al (2017) Human cytomegalovirus triggers the assembly of AIM2 inflammasome in THP-1-derived macrophages. J Med Virol. doi:10.1002/jmv.24846

  • Jenkins C, Garcia W, Godwin MJ et al (2008) Immunomodulatory properties of a viral homolog of human interleukin-10 expressed by human cytomegalovirus during the latent phase of infection. J Virol 82:3736–3750

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Karrer U, Sierro S, Wagner M et al (2003) Memory inflation: continuous accumulation of antiviral CD8+ T cells over time. J Immunol 170:2022–2029

    Article  CAS  PubMed  Google Scholar 

  • Kern F, Faulhaber N, Frömmel C et al (2000) Analysis of CD8 T cell reactivity to cytomegalovirus using protein-spanning pools of overlapping pentadecapeptides. Eur J Immunol 30:1676–1682

    Article  CAS  PubMed  Google Scholar 

  • Khairallah C, Déchanet-Merville J, Capone M (2017) γδ T cell-mediated immunity to cytomegalovirus infection. Front Immunol 8:105

    Article  PubMed  PubMed Central  Google Scholar 

  • Khan N, Shariff N, Cobbold M et al (2002) Cytomegalovirus seropositivity drives the CD8 T cell repertoire toward greater clonality in healthy elderly individuals. J Immunol 169:1984–1992

    Article  CAS  PubMed  Google Scholar 

  • Klenerman P, Hill A (2005) T cells and viral persistence: lessons from diverse infections. Nat Immunol 6:873–879

    Article  CAS  PubMed  Google Scholar 

  • Klenerman P, Oxenius A (2016) T cell responses to cytomegalovirus. Nat Rev Immunol 16:367–377

    Article  CAS  PubMed  Google Scholar 

  • Kothari A, Ramachandran VG, Gupta P et al (2002) Seroprevalence of cytomegalovirus among voluntary blood donors in Delhi, India. J Health Popul Nutr 20:348–351

    PubMed  Google Scholar 

  • Krol L, Stuchl\`y J, Hubáček P et al (2011) Signature profiles of CMV-specific T-cells in patients with CMV reactivation after hematopoietic SCT. Bone Marrow Transplant 46:1089–1098

    Article  CAS  PubMed  Google Scholar 

  • Krug A, French AR, Barchet W et al (2004) TLR9-dependent recognition of MCMV by IPC and DC generates coordinated cytokine responses that activate antiviral NK cell function. Immunity 21:107–119

    Article  CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lachmann R, Bajwa M, Vita S et al (2012) Polyfunctional T cells accumulate in large human cytomegalovirus-specific T cell responses. J Virol 86:1001–1009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lang A, Nikolich-Zugich J (2011) Functional CD8 T cell memory responding to persistent latent infection is maintained for life. J Immunol 187:3759–3768

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Larsen M, Sauce D, Arnaud L et al (2012) Evaluating cellular polyfunctionality with a novel polyfunctionality index. PLoS One 7:e42403

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lelic A, Verschoor CP, Ventresca M et al (2012) The polyfunctionality of human memory CD8+ T cells elicited by acute and chronic virus infections is not influenced by age. PLoS Pathog 8:e1003076

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lichtner M, Cicconi P, Vita S et al (2015) Cytomegalovirus coinfection is associated with an increased risk of severe non-AIDS-defining events in a large cohort of HIV-infected patients. J Infect Dis 211:178–186

    Article  CAS  PubMed  Google Scholar 

  • Lio C-WJ, McDonald B, Takahashi M et al (2016) cGAS-STING signaling regulates initial innate control of cytomegalovirus infection. J Virol 90:7789–7797

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu H, Andreansky S, Diaz G et al (2003) Quantitative analysis of long-term virus-specific CD8+−T-cell memory in mice challenged with unrelated pathogens. J Virol 77:7756–7763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu X-F, Yan S, Abecassis M, Hummel M (2008) Establishment of murine cytomegalovirus latency in vivo is associated with changes in histone modifications and recruitment of transcriptional repressors to the major immediate-early promoter. J Virol 82:10922–10931

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marandu TF, Oduro JD, Borkner L et al (2015) Immune protection against virus challenge in aging mice is not affected by latent herpesviral infections. J Virol 89:11715–11717

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McGeoch DJ, Cook S, Dolan A et al (1995) Molecular phylogeny and evolutionary timescale for the family of mammalian herpesviruses. J Mol Biol 247:443–458

    Article  CAS  PubMed  Google Scholar 

  • Miller J, van der Most RG, Akondy RS et al (2008) Human effector and memory CD8+ T cell responses to smallpox and yellow fever vaccines. Immunity 28:710–722

    Article  CAS  PubMed  Google Scholar 

  • Moreau J-F, Pradeu T, Grignolio A et al (2017) The emerging role of ECM crosslinking in T cell mobility as a hallmark of immunosenescence in humans. Ageing Res Rev 35:322–335

    Article  CAS  PubMed  Google Scholar 

  • Mueller SN, Ahmed R (2009) High antigen levels are the cause of T cell exhaustion during chronic viral infection. Proc Natl Acad Sci U S A 106:8623–8628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Muntasell A, Vilches C, Angulo A, López-Botet M (2013) Adaptive reconfiguration of the human NK-cell compartment in response to cytomegalovirus: a different perspective of the host-pathogen interaction. Eur J Immunol 43:1133–1141

    Article  CAS  PubMed  Google Scholar 

  • Murphy JC, Fischle W, Verdin E, Sinclair JH (2002) Control of cytomegalovirus lytic gene expression by histone acetylation. EMBO J 21:1112–1120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nikolich-Žugich J, Li G, Uhrlaub JL et al (2012) Age-related changes in CD8 T cell homeostasis and immunity to infection. Semin Immunol 24:356–364

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nitzsche A, Paulus C, Nevels M (2008) Temporal dynamics of cytomegalovirus chromatin assembly in productively infected human cells. J Virol 82:11167–11180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Olsson J, Wikby A, Johansson B et al (2000) Age-related change in peripheral blood T-lymphocyte subpopulations and cytomegalovirus infection in the very old: the Swedish longitudinal OCTO immune study. Mech Ageing Dev 121:187–201

    Article  CAS  PubMed  Google Scholar 

  • Oshansky CM, Gartland AJ, Wong S-S et al (2014) Mucosal immune responses predict clinical outcomes during influenza infection independently of age and viral load. Am J Respir Crit Care Med 189:449–462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ouyang Q, Wagner WM, Zheng W et al (2004) Dysfunctional CMV-specific CD8(+) T cells accumulate in the elderly. Exp Gerontol 39:607–613

    Article  CAS  PubMed  Google Scholar 

  • Pawelec G, Akbar A, Caruso C et al (2004) Is immunosenescence infectious? Trends Immunol 25:406–410

    Article  CAS  PubMed  Google Scholar 

  • Pawelec G, McElhaney JE, Aiello AE, Derhovanessian E (2012) The impact of CMV infection on survival in older humans. Curr Opin Immunol 24:507–511

    Article  CAS  PubMed  Google Scholar 

  • Portevin D, Moukambi F, Mpina M et al (2015) Maturation and Mip-1β production of cytomegalovirus-specific T cell responses in Tanzanian children, adolescents and adults: impact by HIV and mycobacterium tuberculosis co-infections. PLoS One 10:e0126716

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pourgheysari B, Khan N, Best D et al (2007) The cytomegalovirus-specific CD4+ T-cell response expands with age and markedly alters the CD4+ T-cell repertoire. J Virol 81:7759–7765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pyzik M, Gendron-Pontbriand E-M, Vidal SM (2011) The impact of Ly49-NK cell-dependent recognition of MCMV infection on innate and adaptive immune responses. J Biomed Biotechnol 2011:641702

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rathinam VAK, Jiang Z, Waggoner SN et al (2010) The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nat Immunol 11:395–402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Redeker A, Welten SPM, Arens R (2014) Viral inoculum dose impacts memory T-cell inflation. Eur J Immunol 44:1046–1057

    Article  CAS  PubMed  Google Scholar 

  • Reese TA, Bi K, Kambal A et al (2016) Sequential infection with common pathogens promotes human-like immune gene expression and altered vaccine response. Cell Host Microbe 19:713–719

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reese TA, Wakeman BS, Choi HS et al (2014) Helminth infection reactivates latent γ-herpesvirus via cytokine competition at a viral promoter. Science 345:573–577

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Remmerswaal EBM, Havenith SHC, Idu MM et al (2012) Human virus-specific effector-type T cells accumulate in blood but not in lymph nodes. Blood 119:1702–1712

    Article  CAS  PubMed  Google Scholar 

  • Riddell NE, Griffiths SJ, Rivino L et al (2015) Multifunctional cytomegalovirus (CMV)-specific CD8+ T cells are not restricted by telomere-related senescence in young or old adults. Immunology 144:549–560

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roux A, Mourin G, Larsen M et al (2013) Differential impact of age and cytomegalovirus infection on the γδ T cell compartment. J Immunol 191:1300–1306

    Article  CAS  PubMed  Google Scholar 

  • Sandalova E, Laccabue D, Boni C et al (2010) Contribution of herpesvirus specific CD8 T cells to anti-viral T cell response in humans. PLoS Pathog 6:e1001051

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sauce D, Gorochov G, Larsen M (2016) HIV-specific Th2 and Th17 responses predict HIV vaccine protection efficacy. Sci Rep 6:28129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Selin LK, Lin MY, Kraemer KA et al (1999) Attrition of T cell memory: selective loss of LCMV epitope-specific memory CD8 T cells following infections with heterologous viruses. Immunity 11:733–742

    Article  CAS  PubMed  Google Scholar 

  • Selin LK, Vergilis K, Welsh RM, Nahill SR (1996) Reduction of otherwise remarkably stable virus-specific cytotoxic T lymphocyte memory by heterologous viral infections. J Exp Med 183:2489–2499

    Article  CAS  PubMed  Google Scholar 

  • Sester M, Sester U, Gärtner B et al (2002) Sustained high frequencies of specific CD4 T cells restricted to a single persistent virus. J Virol 76:3748–3755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shaw AC, Goldstein DR, Montgomery RR (2013) Age-dependent dysregulation of innate immunity. Nat Rev Immunol 13:875–887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sinclair JH, Reeves MB (2013) Human cytomegalovirus manipulation of latently infected cells. Viruses 5:2803–2824

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Snyder CM, Cho KS, Bonnett EL et al (2008) Memory inflation during chronic viral infection is maintained by continuous production of short-lived, functional T cells. Immunity 29:650–659

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sohlberg E, Saghafian-Hedengren S, Rasul E et al (2013) Cytomegalovirus-seropositive children show inhibition of in vitro EBV infection that is associated with CD8+ CD57+ T cell enrichment and IFN-γ. J Immunol 191:5669–5676

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Solana R, Tarazona R, Aiello AE et al (2012) CMV and immunosenescence: from basics to clinics. Immun Ageing 9:23

    Article  PubMed  PubMed Central  Google Scholar 

  • Sylwester AW, Mitchell BL, Edgar JB 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tabeta K, Georgel P, Janssen E et al (2004) Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection. Proc Natl Acad Sci U S A 101:3516–3521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Taylor-Wiedeman J, Sissons P, Sinclair J (1994) Induction of endogenous human cytomegalovirus gene expression after differentiation of monocytes from healthy carriers. J Virol 68:1597–1604

    CAS  PubMed  PubMed Central  Google Scholar 

  • Terrazzini N, Bajwa M, Vita S et al (2014) A novel cytomegalovirus-induced regulatory-type T-cell subset increases in size during older life and links virus-specific immunity to vascular pathology. J Infect Dis 209:1382–1392

    Article  CAS  PubMed  Google Scholar 

  • Trzonkowski P, Myśliwska J, Szmit E et al (2003) Association between cytomegalovirus infection, enhanced proinflammatory response and low level of anti-hemagglutinins during the anti-influenza vaccination—an impact of immunosenescence. Vaccine 21:3826–3836

    Article  CAS  PubMed  Google Scholar 

  • van de Berg PJ, Heutinck KM, Raabe R et al (2010) Human cytomegalovirus induces systemic immune activation characterized by a type 1 cytokine signature. J Infect Dis 202:690–699

    Article  PubMed  CAS  Google Scholar 

  • van der Heiden M, van Zelm MC, Bartol SJW et al (2016) Differential effects of Cytomegalovirus carriage on the immune phenotype of middle-aged males and females. Sci Rep 6:26892

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • van Leeuwen EMM, Koning JJ, Remmerswaal EBM et al (2006) Differential usage of cellular niches by cytomegalovirus versus EBV- and influenza virus-specific CD8+ T cells. J Immunol 177:4998–5005

    Article  PubMed  Google Scholar 

  • Van Lier RAW, Ten Berge IJM, Gamadia LE (2003) Human CD8+ T-cell differentiation in response to viruses. Nat Rev Immunol 3:931–939

    Article  PubMed  Google Scholar 

  • Varani S, Cederarv M, Feld S et al (2007) Human cytomegalovirus differentially controls B cell and T cell responses through effects on plasmacytoid dendritic cells. J Immunol 179:7767–7776

    Article  CAS  PubMed  Google Scholar 

  • Virgin HW, Wherry EJ, Ahmed R (2009) Redefining chronic viral infection. Cell 138:30–50

    Article  CAS  PubMed  Google Scholar 

  • Voigt V, Forbes CA, Tonkin JN et al (2003) Murine cytomegalovirus m157 mutation and variation leads to immune evasion of natural killer cells. Proc Natl Acad Sci U S A 100:13483–13488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang GC, Dash P, McCullers JA et al (2012) T cell receptor αβ diversity inversely correlates with pathogen-specific antibody levels in human cytomegalovirus infection. Sci Transl Med 4:128ra42

    PubMed  PubMed Central  Google Scholar 

  • Wertheimer AM, Bennett MS, Park B et al (2014) Aging and cytomegalovirus infection differentially and jointly affect distinct circulating T cell subsets in humans. J Immunol 192:2143–2155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wherry EJ, Kurachi M (2015) Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol 15:486–499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • White DW, Keppel CR, Schneider SE et al (2010) Latent herpesvirus infection arms NK cells. Blood 115:4377–4383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Whiting CC, Siebert J, Newman AM et al (2015) Large-scale and comprehensive immune profiling and functional analysis of normal human aging. PLoS One 10:e0133627

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zaia JA, Sun JY, Gallez-Hawkins GM et al (2009) The effect of single and combined activating killer immunoglobulin-like receptor genotypes on cytomegalovirus infection and immunity after hematopoietic cell transplantation. Biol Blood Marrow Transplant 15:315–325

    Article  PubMed  PubMed Central  Google Scholar 

  • Zucchini N, Bessou G, Traub S et al (2008) Cutting edge: overlapping functions of TLR7 and TLR9 for innate defense against a herpesvirus infection. J Immunol 180:5799–5803

    Article  CAS  PubMed  Google Scholar 

  • Zuniga EI, Harker JA (2012) T-cell exhaustion due to persistent antigen: quantity not quality? Eur J Immunol 42:2285–2289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Aisha Souquette & Paul G. Thomas

  2. Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), INSERM U1135, Sorbonne Universités, UPMC DHU FAST, Paris, France

    Justin Frere & Delphine Sauce

  3. Arizona Center on Aging, Department of Immunobiology, University of Arizona, Tucson, AZ, USA

    Justin Frere & Megan Smithey

Authors
  1. Aisha Souquette
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Justin Frere
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Megan Smithey
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Delphine Sauce
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paul G. Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paul G. Thomas.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Souquette, A., Frere, J., Smithey, M. et al. A constant companion: immune recognition and response to cytomegalovirus with aging and implications for immune fitness. GeroScience 39, 293–303 (2017). https://doi.org/10.1007/s11357-017-9982-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11357-017-9982-x

Keywords

Search

Navigation