Lower proportion of naïve peripheral CD8+ T cells and an unopposed pro-inflammatory response to human Cytomegalovirus proteins in vitro are associated with longer survival in very elderly people

Almanzar G, Schwaiger S, Jenewein B, Keller M, Herndler-Brandstetter D, Wurzner R, Schonitzer D, Grubeck-Loebenstein B (2005) Long-term cytomegalovirus infection leads to significant changes in the composition of the CD8+ T-cell repertoire, which may be the basis for an imbalance in the cytokine production profile in elderly persons. J Virol 79:3675–3683

Barker WH, Mullooly JP (1980) Influenza vaccination of elderly persons. Reduction in pneumonia and influenza hospitalizations and deaths. Jama 244:2547–2549

Campitelli MA, Rosella LC, Stukel TA, Kwong JC (2010) Influenza vaccination and all-cause mortality in community-dwelling elderly in Ontario, Canada, a cohort study. Vaccine 29:240–246

Chidrawar S, Khan N, Wei W, McLarnon A, Smith N, Nayak L, Moss P (2009) Cytomegalovirus-seropositivity has a profound influence on the magnitude of major lymphoid subsets within healthy individuals. Clin Exp Immunol 155:423–432

Cook CH, Yenchar JK, Kraner TO, Davies EA, Ferguson RM (1998) Occult herpes family viruses may increase mortality in critically ill surgical patients. Am J Surg 176:357–360

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

Crough T, Fazou C, Weiss J, Campbell S, Davenport MP, Bell SC, Galbraith A, McNeil K, Khanna R (2007) Symptomatic and asymptomatic viral recrudescence in solid-organ transplant recipients and its relationship with the antigen-specific CD8(+) T-cell response. J Virol 81:11538–11542

Derhovanessian E, Larbi A, Pawelec G (2009) Biomarkers of human immunosenescence: impact of Cytomegalovirus infection. Curr Opin Immunol 21:440–445

Derhovanessian E, Maier AB, Beck R, Jahn G, Hahnel K, Slagboom PE, de Craen AJ, Westendorp RG, Pawelec G (2010) Hallmark features of immunosenescence are absent in familial longevity. J Immunol 185:4618–4624

Faint JM, Annels NE, Curnow SJ, Shields P, Pilling D, Hislop AD, Wu L, Akbar AN, Buckley CD, Moss PA, Adams DH, Rickinson AB, Salmon M (2001) Memory T cells constitute a subset of the human CD8+ CD45RA+ pool with distinct phenotypic and migratory characteristics. J Immunol 167:212–220

Ferguson FG, Wikby A, Maxson P, Olsson J, Johansson B (1995) Immune parameters in a longitudinal study of a very old population of Swedish people: a comparison between survivors and nonsurvivors. J Gerontol A Biol Sci Med Sci 50:B378–B382

Folstein MF, Folstein SE, McHugh PR (1975) Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198

Franceschi C (2007) Inflammaging as a major characteristic of old people: can it be prevented or cured? Nutr Rev 65:S173–S176

Franceschi C, Monti D, Barbieri D, Grassilli E, Troiano L, Salvioli S, Negro P, Capri M, Guido M, Azzi R et al (1995) Immunosenescence in humans: deterioration or remodelling? Int Rev Immunol 12:57–74

Ganepola S, Gentilini C, Hilbers U, Lange T, Rieger K, Hofmann J, Maier M, Liebert UG, Niederwieser D, Engelmann E, Heilbronn R, Thiel E, Uharek L (2007) Patients at high risk for CMV infection and disease show delayed CD8+ T-cell immune recovery after allogeneic stem cell transplantation. Bone Marrow Transplant 39:293–299

Gilden DH, Cohrs RJ, Mahalingam R (2003) Clinical and molecular pathogenesis of varicella virus infection. Viral Immunol 16:243–258

Gruver AL, Hudson LL, Sempowski GD (2007) Immunosenescence of ageing. J Pathol 211:144–156

Hadrup SR, Strindhall J, Kollgaard T, Seremet T, Johansson B, Pawelec G, thor Straten P, Wikby A (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

Jaber S, Chanques G, Borry J, Souche B, Verdier R, Perrigault PF, Eledjam JJ (2005) Cytomegalovirus infection in critically ill patients: associated factors and consequences. Chest 127:233–241

Kempen GI, Miedema I, Ormel J, Molenaar W (1996) The assessment of disability with the Groningen Activity Restriction Scale. Conceptual framework and psychometric properties. Soc Sci Med 43:1601–1610

Lacey SF, Martinez J, Gallez-Hawkins G, Thao L, Longmate J, Haq W, Spielberger R, Forman SJ, Zaia JA, Diamond DJ (2005) Simultaneous reconstitution of multiple cytomegalovirus-specific CD8+ cell populations with divergent functionality in hematopoietic stem-cell transplant recipients. J Infect Dis 191:977–984

Limaye AP, Kirby KA, Rubenfeld GD, Leisenring WM, Bulger EM, Neff MJ, Gibran NS, Huang ML, Santo Hayes TK, Corey L, Boeckh M (2008) Cytomegalovirus reactivation in critically ill immunocompetent patients. Jama 300:413–422

Malaguarnera L, Cristaldi E, Malaguarnera M (2010) The role of immunity in elderly cancer. Crit Rev Oncol Hematol 74:40–60

McElhaney JE, Effros RB (2009) Immunosenescence: what does it mean to health outcomes in older adults? Curr Opin Immunol 21:418–424

Murasko DM, Weiner P, Kaye D (1988) Association of lack of mitogen-induced lymphocyte proliferation with increased mortality in the elderly. Aging Immunol Infect Dis 1:1–6

Nebbia G, Mattes FM, Smith C, Hainsworth E, Kopycinski J, Burroughs A, Griffiths PD, Klenerman P, Emery VC (2008) Polyfunctional cytomegalovirus-specific CD4+ and pp 65 CD8+ T cells protect against high-level replication after liver transplantation. Am J Transplant 8:2590–2599

Nichol KL, Nordin J, Mullooly J, Lask R, Fillbrandt K, Iwane M (2003) Influenza vaccination and reduction in hospitalizations for cardiac disease and stroke among the elderly. N Engl J Med 348:1322–1332

Nichol KL, Nordin JD, Nelson DB, Mullooly JP, Hak E (2007) Effectiveness of influenza vaccine in the community-dwelling elderly. N Engl J Med 357:1373–1381

Olsson J, Wikby A, Johansson B, Lofgren S, Nilsson BO, Ferguson FG (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

Pawelec G, Derhovanessian E (2011) Role of CMV in immune senescence. Virus Res 157:175–179

Pawelec G, Derhovanessian E, Larbi A, Strindhall J, Wikby A (2009) Cytomegalovirus and human immunosenescence. Rev Med Virol 19:47–56

Roberts ET, Haan MN, Dowd JB, Aiello AE (2010) Cytomegalovirus antibody levels, inflammation, and mortality among elderly Latinos over 9 years of follow-up. Am J Epidemiol 172:363–371

Romero P, Zippelius A, Kurth I, Pittet MJ, Touvrey C, Iancu EM, Corthesy P, Devevre E, Speiser DE, Rufer N (2007) Four functionally distinct populations of human effector-memory CD8+ T lymphocytes. J Immunol 178:4112–4119

Sansoni P, Vescovini R, Fagnoni F, Biasini C, Zanni F, Zanlari L, Telera A, Lucchini G, Passeri G, Monti D, Franceschi C, Passeri M (2008) The immune system in extreme longevity. Exp Gerontol 43:61–65

Semba RD, Margolick JB, Leng S, Walston J, Ricks MO, Fried LP (2005) T cell subsets and mortality in older community-dwelling women. Exp Gerontol 40:81–87

Simanek AM, Dowd JB, Pawelec G, Melzer D, Dutta A, Aiello AE (2011) Seropositivity to cytomegalovirus, inflammation, all-cause and cardiovascular disease-related mortality in the United States. PLoS One 6:e16103

Stowe RP, Kozlova EV, Yetman DL, Walling DM, Goodwin JS, Glaser R (2007) Chronic herpesvirus reactivation occurs in aging. Exp Gerontol 42:563–570

Strandberg TE, Pitkala KH, Tilvis RS (2009) Cytomegalovirus antibody level and mortality among community-dwelling older adults with stable cardiovascular disease. Jama 301:380–382

van der Wiel AB, van Exel E, de Craen AJ, Gussekloo J, Lagaay AM, Knook DL, Westendorp RG (2002) A high response is not essential to prevent selection bias: results from the Leiden 85-plus study. J Clin Epidemiol 55:1119–1125

Wayne SJ, Rhyne RL, Garry PJ, Goodwin JS (1990) Cell-mediated immunity as a predictor of morbidity and mortality in subjects over 60. J Gerontol 45:M45–M48

Wijsman CA, Maier AB, de Craen AJ, van den Biggelaar AH, Westendorp RG (2011) An unopposed proinflammatory response is beneficial for survival in the oldest old. Results of the Leiden 85-plus study. J Gerontol A Biol Sci Med Sci 66:393–399

Wikby A, Maxson P, Olsson J, Johansson B, Ferguson FG (1998) Changes in CD8 and CD4 lymphocyte subsets. T cell proliferation responses and non-survival in the very old: the Swedish longitudinal OCTO-immune study. Mech Ageing Dev 102:187–198

Wikby A, Johansson B, Olsson J, Lofgren S, Nilsson BO, Ferguson F (2002) Expansions of peripheral blood CD8 T-lymphocyte subpopulations and an association with cytomegalovirus seropositivity in the elderly: the Swedish NONA immune study. Exp Gerontol 37:445–453

Wikby A, Ferguson F, Forsey R, Thompson J, Strindhall J, Lofgren S, Nilsson BO, Ernerudh J, Pawelec G, Johansson B (2005) An immune risk phenotype, cognitive impairment, and survival in very late life: impact of allostatic load in Swedish octogenarian and nonagenarian humans. J Gerontol A Biol Sci Med Sci 60:556–565

Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, Leirer VO (1982) Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res 17:37–49