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The Immune Risk Profile and Associated Parameters in Late Life: Lessons from the OCTO and NONA Longitudinal Studies

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Handbook on Immunosenescence

Abstract

The OCTO Immune Longitudinal Study is a population-based study of ageing in a sample of 102 Swedish octogenarians with the aim to explore age changes of the immune system using a sample selected for good health. Data collection was performed in 1989, 1990, 1991 and 1997. An Immune Risk Profile (IRP) associated with increased mortality was characterized by high CD8+, low CD4+ T-cell counts and a poor T-cell proliferative response, inversion of the CD4/CD8 ratio and evidence of persistent cytomegalovirus infection was identified. The subsequent NONA Immune Longitudinal Study of 138 Swedish nonagenarians was performed in 1999, 2001, 2003, and 2005, not excluding individuals due to compromised health. The overall aim was to examine predictive factors for longevity and to further investigate in greater depth the immune risk profile identified in the OCTO Immune Study in the context of functional and disability parameters also examined in the NONA. The immune panel included the analysis of T-cell subsets, inflammatory markers, virus serology, cytokines, TCR clonotype mapping, and functional and phenotypic analysis of virus specific CD8+ cells by HLA/peptide multimers, in collaborations between participants of the EU funded T-CIA project.

The present chapter report findings from the longitudinal studies of Swedish octo-nonagenarians with focus on IRP and its associations with persistent virus infection, CD8+ T-cell differentiation, cytokines, cognitive functioning, inflammatory activity, virus specific CD8+ cells, CD8+ T-cell clonal expansions and longevity. It also reports on low grade inflammation processes of importance in predicting longevity in the very late life.

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References

  • Akbar AN, Fletcher JM (2005) Memory T-cell homeostasis and senescence during aging. Curr. Opin Immunol 17:480–485

    Article  CAS  Google Scholar 

  • Appay V, Dunbar PR, Callan M et al (2002) Memory CD8+ T-cells vary in differentiation phenotype in different persistent virus infections. Nat Med 8:379–385

    Article  PubMed  CAS  Google Scholar 

  • Bruunsgaard H, Ladelund S, Pedersen AN, Schroll M, Jorgensen T, Pedersen BK (2003) Predicting death from tumour necrosis factor-alpha and interleukin-6 in 80-year-old people. Clin Exp Immunol 132:24–31

    Article  PubMed  CAS  Google Scholar 

  • Delarosa O, Pawelec G, Peralbo E, Wikby A, Mariani E, Mocchegiani E, Tarazona R, Solana R (2006) Immunological biomarkers of ageing in man; changes in both innate and adaptive immunity are associated with health and longevity. Biogerontology 7:471–481

    Article  PubMed  CAS  Google Scholar 

  • Effros R (2004) From Hayflick to Walford: the role of T-cell replicative senescence in human aging. Exp Gerontol 39:885–890

    Article  PubMed  CAS  Google Scholar 

  • Effros RB (2007) Role of T-lymphocyte replicative senescence in vaccine efficacy. Vaccine 25:599–604

    Article  PubMed  CAS  Google Scholar 

  • Evrin PE, Nilsson SE, Öberg T, Malmberg B (2005) Serum C-reactive protein in elderly men and women: association with mortality, morbidity and various biochemical values. Scand J Clin Lab Invest 65:23–31

    Article  PubMed  CAS  Google Scholar 

  • 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 of survivors and nonsurvivors. J Gerontol Biol Sci 50A:B378–B382

    Google Scholar 

  • Fletcher JM, Vukmanovic-Stejic M, Dunne PJ, Birch KE, Cook JE, Jackson SE, Salmon M, Rustin MH, Akbar AN (2005) Cytomegalovirus-specific CD4 +T-cells in healthy carriers are continuously driven to replicative exhaustion. J Immunol 175:8218–8225

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Forsey RJ, Thompson JM, Ernerudh J, Hurst TL, Strindhall J, Johansson B, Nilsson BO, Wikby A (2003) Plasma cytokine profiles in elderly humans. Mech Ageing Dev 124:487–493

    Article  PubMed  CAS  Google Scholar 

  • Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G (2000) Inflamm-aging: an evolutionary perspective on immunosenescence. Ann NY Acad Sci 908:244–254

    Article  PubMed  CAS  Google Scholar 

  • Fulop T, Larbi A, Wikby A, Mocchegiani E, Hirokawa K, Pawelec G (2005) Dysregulation of T-cell function in the elderly: scientific basis and clinical implications. Drugs Aging 22:589–603

    Article  PubMed  Google Scholar 

  • Goronzy JJ, Fulbright JW, Crowson CS, Poland GA, O’Fallon WM, Weyand CM (2001) Value of immunological markers in predicting responsiveness to influenza vaccination in elderly individuals. J Virol 75:12182–12187

    Article  PubMed  CAS  Google Scholar 

  • Hallgren HM, Bergh N, Rodysill KJ, O’Leary JJ (1988) Lymphocyte proliferative response to PHA and anti-CD3/Ti monoclonal antibodies, T-cell surface marker expression, and serum IL-2 receptor levels as biomarkers of age and health. Mech Ageing Dev 43:175–185

    Article  PubMed  CAS  Google Scholar 

  • Huppert FA, Pinto EM, Morgan K, Brayne C (2003) Survival in a population sample is predicted by proportions of lymphocyte subsets. Mech Ageing Dev 124:449–451

    Article  PubMed  Google Scholar 

  • Jeune B (2002) Living longer—but better? Aging Clin Exp Res 14:72–93

    PubMed  Google Scholar 

  • Johansson B (1988/89) The MIR—Memory in Reality Test. Stockholm, Sweden: Psykologiförlaget AB

    Google Scholar 

  • Johansson B, Zarit SH, Berg S (1992) Changes in cognitive functioning of the oldest old. J Gerontol 47:P75–P80

    PubMed  CAS  Google Scholar 

  • Johansson B, Zarit SH (1997) Early cognitive markers of the incidence of dementia and mortality: a longitudinal population-based study of the oldest old. Int J Geriatr Psychiatry 12:53–59

    Article  PubMed  CAS  Google Scholar 

  • Khan N, Shariff N, Cobbold M, Bruton R, Ainsworth, JA, Sinclair AJ, Nayak L, Moss PA (2002) Cytomegalovirus seropositivity drives the CD8 T-cell repertoire toward greater clonality in healthy elderly individuals. J Immunol 169:1984–1992

    PubMed  CAS  Google Scholar 

  • Khan N, Hislop A, Gudgeon N, Cobbold M, Khanna R, Nayak L, Rickinson AB, Moss PA (2004) Herpesvirus-specific CD8 T-cell immunity in old age: cytomegalovirus impairs the response to a coresident EBV infection. J Immunol 173:7481–7489

    PubMed  CAS  Google Scholar 

  • Karlamangla AS, Singer BH, McEwen BS, Rowe JW, Seeman TE (2002) Allostatic load as a predictor of functional decline: MacArthur studies of successful aging. J Clin Epidemiol 55:696–710

    Article  PubMed  Google Scholar 

  • Karlamangla AS, Singer BH, Seeman TE (2006) Reduction in allostatic load in older adults is associated with lower all-cause mortality risk: MacArthur studies of successful aging. Psychosom Med 68:500–507

    Article  PubMed  Google Scholar 

  • Koch S, Kempf J, Pawelec G (2005) T-CIA: investigating T-cells in aging. Sci Aging Knowledge Environ:pe21

    Google Scholar 

  • Krabbe KS, Pedersen M, Bruunsgaard H (2004) Inflammatory mediators in the elderly. Exp Gerontol 39:687–699

    Article  PubMed  CAS  Google Scholar 

  • Ligthart GJ, Corberand JX, Fournier C, Galanaud P, Hijmans W, Kennes B, Muller-Hermelink HK, Steinmann GG (1984) Admission criteria for immunogerontological studies in man: the SENIEUR protocol. Mech Ageing Dev 28:47–55

    Article  PubMed  CAS  Google Scholar 

  • McEwen BS, Stellar E (1993) Stress and the individual: mechanisms leading to disease. Arch Intern Med 153:2093–2101

    Article  PubMed  CAS  Google Scholar 

  • McEwen BS (2003) Interacting mediators of allostasis and allostatic load: towards an understanding of resilience in aging. Metabolism 52:10–16

    Article  PubMed  CAS  Google Scholar 

  • Marsland AL, Petersen KL, Sathanoori R, Muldoon MF, Neumann SA, Ryan C, Flory JD, Manuck SB (2006) Interleukin-6 covaries inversely with cognitive performance among middle-aged community volunteers. Psychosom Med 68:895–903

    Article  PubMed  CAS  Google Scholar 

  • Messaoudi I, Lemaoult J, Guevara-Patino JA, Metzner BM, Nikolich-Zugich J (2004) Age-related CD8 T-cell clonal expansions constrict CD8 T-cell repertoire and have the potential to impair immune defence. J Exp Med 200:1347–1358

    Article  PubMed  CAS  Google Scholar 

  • Miller RA (2001) Biomarkers of aging: prediction of longevity by using age-sensitive T-cell subset determinations in a middle-aged, genetically heterogeneous mouse population. J Gerontol Biol Sci 56 A:B180–B186

    Google Scholar 

  • Moss P, Khan N (2004) CD8+ T-cell immunity to cytomegalovirus. Human Immunol 65:456–464

    Article  CAS  Google Scholar 

  • Murasko DM, Weiner P, Kaye D (1987) Decline in mitogen induced proliferation of lymphocytes with increasing age. Clin Exp Immunol 70:440–448

    PubMed  CAS  Google Scholar 

  • Nilsson BO, Ernerudh J, Johansson B, Evrin P-E, Löfgren S, Ferguson F, Wikby A (2003) Morbidity does not influence the T-cell immune risk phenotype in the elderly: findings in the Swedish NONA Immune Study using sample selection protocols. Mech Ageing Dev 124:469–476

    Article  PubMed  Google Scholar 

  • Olsson J, Wikby A, Johansson B, Löfgren S, Nilsson B-O, Ferguson F (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  PubMed  CAS  Google Scholar 

  • Ouyang Q, Wagner WM, Walter S, Muller CA, Wikby A, Aubert G, Klatt T, Stevanovic S, Dodi T, Pawelec G (2003). An age-related increase in the number of CD8+ T-cells carrying receptors for an immunodominant Epstein-Barr virus (EBV) epitope is counteracted by a decreased frequency of their antigen-specific responsiveness. Mech Ageing Dev 124:477–485

    Article  PubMed  CAS  Google Scholar 

  • Ouyang Q, Wagner WM, Zheng W, Wikby A, Remarque EJ, Pawelec G (2004) Dysfunctional CMV-specific CD8+ T-cells accumulate in the elderly. Exp Gerontol 39:607–613

    Article  PubMed  CAS  Google Scholar 

  • Pawelec G, Ferguson F, Wikby A (2001) The SENIEUR protocol after 16 years. Mech Ageing Dev 122:132–134

    Article  PubMed  CAS  Google Scholar 

  • Pawelec G, Caruso C (2003) Immunology and ageing in Europe: ImAginE-ation in the EU. Mech Ageing Dev 124:357–360

    Article  PubMed  Google Scholar 

  • Pawelec G, Akbar A, Caruso C, Grubeck-Loebenstein B, Solana R, Wikby A (2005) Human immunosenescence: is it infectious? Immunol Rev 205:257–268

    Article  PubMed  CAS  Google Scholar 

  • Pawelec G (2006) Immunity and ageing in man. Exp Gerontol 41:1239–1242

    Article  PubMed  CAS  Google Scholar 

  • Pourgheysari B, Khan N, Best D, Bruton R, Nayak L, Moss PA (2007) The CMV-specific CD4+ T-cell response expands with age and markedly alters the CD4+ T-cell repertoire. J Virol 81:7759–7765

    Article  PubMed  CAS  Google Scholar 

  • Reker-Hadrup S, 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 cytomegalovirusspecific T-cells in the very elderly. J Immunol 176:2645–2653

    Google Scholar 

  • Reuben DB, Cheh AI, Harris TB, Ferrucci L, Rowe JW, Tracy RP, Seeman TE (2002) Peripheral blood markers of inflammation predict mortality and functional decline in high-functioning community-dwelling older persons. J Am Geriatr Soc 50:638–644

    Article  PubMed  Google Scholar 

  • Roberts-Thomson IC, Whittingham S, Youngchaiyud U, Mackay IR (1974). Ageing, immune response and mortality. Lancet 2:368–370

    Article  PubMed  CAS  Google Scholar 

  • Saurwein-Teissl M, Lung TL, Marx F, Gschösser C, Asch E, Blasko I, Parson W, Böck G, Schönitzer D, Trannoy E, Grubeck-Loebenstein B (2002) Lack of antibody production following immunization in old age: association with CD8+CD28-T-cell clonal expansions and an imbalance in the production of Th1 and Th2 cytokines. J Immunol 168:5893–5899

    PubMed  CAS  Google Scholar 

  • Steensberg A., Fischer CP, Keller C, Moller K, Pedersen BK (2003) IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. Am J Physiol Endocrinol Metab 285:E433–E437

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Strindhall J, Nilsson BO, Löfgren S, Ernerudh J, Pawelec G, Johansson B, Wikby A (2007) No immune risk profile among individuals who reach 100 years of age: Findings from the Swedish NONA immune longitudinal study. Exp Gerontol 42:753–761

    Article  PubMed  CAS  Google Scholar 

  • Tarkowski E (2002) Cytokines in dementias. Curr Drug Targets Inflamm Allergy 1:193–200

    Article  PubMed  CAS  Google Scholar 

  • thor Straten P, Barfoed A, Seremet T, Saeterdal I, Zeuthen J, Guldberg P (1998) Detection and characterization of alpha-beta-T-cell clonality by denaturing gradient gel electrophoresis (DGGE). Biotechniques 25:244–250

    Google Scholar 

  • Trzonkowski P, Mysliwska J, Szmit E, Wieckiewicz J, Lukaszuk K, Brydak LB, Machala M, Mysliwski A (2003) Associations between cytomegalovirus infection, enhanced proinflammatory response and low levels of antihemagglutinins during the antiinfluenza vaccination—an impact of immunosenescence. Vaccine 21:3826–3836

    Article  PubMed  CAS  Google Scholar 

  • Wallace DL, Zhang Y, Ghattas H, Worth A, Irvine A, Bennett AR, Griffin GE, Beverley PC, Tough DF, Macallan DC (2004) Direct measurement of T-cell subset kinetics in vivo in elderly men and women. J Immunol 173;1787–1794

    PubMed  CAS  Google Scholar 

  • 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 Med Sci 45:M45–M48

    Article  CAS  Google Scholar 

  • Vasto S, Colonna-Romano G, Larbi A, Wikby A, Caruso C, Pawelec G (2007) Role of persistent CMV infection in configuring T-cells immunity in the elderly. Immun Ageing 4:2

    Article  PubMed  CAS  Google Scholar 

  • Wikby A, Johansson B, Ferguson F, Olsson J (1994) Age-related changes in immune parameters in a very old population of Swedish people: a longitudinal study. Exp Gerontol 29:531–541

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Wikby A, Johansson B, Olsson J, Löfgren S, Nilsson B-O, 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

    Article  PubMed  CAS  Google Scholar 

  • Wikby A, Johansson B, Ferguson F (2003) The OCTO and NONA immune longitudinal studies: a review of 11 years studies of Swedish very old humans. Adv Cell Aging Gerontol 13:1–16

    Article  Google Scholar 

  • Wikby A, Ferguson F, Forsey R, Thompson J, Strindhall J, Löfgren S, Nilsson B-O, 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 Biol Sci 60A:556–565

    Google Scholar 

  • Wikby A, Nilsson BO, Forsey R, Thompson J, Strindhall J, Löfgren S, Ernerudh J, Pawelec G, Ferguson F, Johansson B (2006) 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

    Article  PubMed  CAS  Google Scholar 

  • Wilson CJ, Finch CE, Cohen HJ (2002) Cytokines and cognition: the case for a head-to-toe inflammation paradigm. J Am Geriatr Soc 50:2041–2056

    Article  PubMed  Google Scholar 

  • Zanni F, Vescovini R, Biasini C, Fagnoni F, Zanlari L, Telera A, Di Pede P, Passeri G, Pedrazzoni M, Passeri M, Franceschi C, Sansoni P (2003) Marked increase with age of Type-1 cytokines within memory and effector/cytotoxic CD8+ T-cells in humans: a contribution to understand the relationship between inflammation and immunosenescence. Exp Gerontol 38:981–987

    Article  PubMed  CAS  Google Scholar 

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Wikby, A., Strindhall, J., Johansson, B. (2009). The Immune Risk Profile and Associated Parameters in Late Life: Lessons from the OCTO and NONA Longitudinal Studies. In: Fulop, T., Franceschi, C., Hirokawa, K., Pawelec, G. (eds) Handbook on Immunosenescence. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-9063-9_1

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