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The role of the T cell in age-related inflammation

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Abstract

Ageing is accompanied by alterations to T-cell immunity and also by a low-grade chronic inflammatory state termed inflammaging. The significance of these phenomena is highlighted by their being predictors of earlier mortality. We have recently published that the proinflammatory cytokine TNFα is a strong inducer of CD4+ T-cell senescence and T-cell differentiation, adding to the growing body of literature implicating proinflammatory molecules in mediating these critical age-related T-cell alterations. Moreover, the inflammatory process is also being increasingly implicated in the pathogenesis of many common and severe age-related diseases, including cancer, cardiovascular diseases and type 2 diabetes. Furthermore, major age-related risk factors for poor health, such as obesity, stress and smoking, are also associated with an upregulation in systemic inflammatory markers. We propose the idea that the ensuing inflammatory response to influenza infection propagates cardiovascular diseases and constitutes a major cause of influenza-related mortality. While inflammation is not a negative phenomenon per se, this age-related dysregulation of inflammatory responses may play crucial roles driving age-related pathologies, T-cell immunosenescence and CMV reactivation, thereby underpinning key features of the ageing process.

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References

  • Abu-Taha M, Rius C, Hermenegildo C, Noguera I, Cerda-Nicolas JM, Issekutz AC, Jose PJ, Cortijo J, Morcillo EJ, Sanz MJ (2009) Menopause and ovariectomy cause a low grade of systemic inflammation that may be prevented by chronic treatment with low doses of estrogen or losartan. J Immunol 183:1393–1402

    PubMed  CAS  Google Scholar 

  • Akbar AN, Henson SM (2011) Are senescence and exhaustion intertwined or unrelated processes that compromise immunity? Nat Rev Immunol 11:289–295

    PubMed  CAS  Google Scholar 

  • Bagnara GP, Bonsi L, Strippoli P, Bonifazi F, Tonelli R, D’Addato S, Paganelli R, Scala E, Fagiolo U, Monti D, Cossarizza A, Bonafe M, Franceschi C (2000) Hemopoiesis in healthy old people and centenarians: well-maintained responsiveness of CD34+ cells to hemopoietic growth factors and remodeling of cytokine network. J Gerontol A Biol Sci Med Sci 55:B61–B66

    PubMed  CAS  Google Scholar 

  • Bakhru A, Erlinger TP (2005) Smoking cessation and cardiovascular disease risk factors: results from the Third National Health and Nutrition Examination Survey. PLoS Med 2:e160

    PubMed  PubMed Central  Google Scholar 

  • Ballou SP, Lozanski FB, Hodder S, Rzewnicki DL, Mion LC, Sipe JD, Ford AB, Kushner I (1996) Quantitative and qualitative alterations of acute-phase proteins in healthy elderly persons. Age Aging 25:224–230

    CAS  Google Scholar 

  • Baur JA, Sinclair DA (2006) Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 5:493–506

    PubMed  CAS  Google Scholar 

  • Baxter R, Lee J, Fireman B (2010) Evidence of bias in studies of influenza vaccine effectiveness in elderly patients. J Infect Dis 201:186–189

    PubMed  Google Scholar 

  • Beenakker KG, Ling CH, Meskers CG, de Craen AJ, Stijnen T, Westendorp RG, Maier AB (2010) Patterns of muscle strength loss with age in the general population and patients with a chronic inflammatory state. Ageing Res Rev 9:431–436

    PubMed  Google Scholar 

  • Birkenkamp KU, Coffer PJ (2003) Regulation of cell survival and proliferation by the FOXO (Forkhead box, class O) subfamily of Forkhead transcription factors. Biochem Soc Trans 31:292–297

    PubMed  CAS  Google Scholar 

  • Bruns H, Meinken C, Schauenberg P, Harter G, Kern P, Modlin RL, Antoni C, Stenger S (2009) Anti-TNF immunotherapy reduces CD8+ T cell-mediated antimicrobial activity against Mycobacterium tuberculosis in humans. J Clin Invest 119:1167–1177

    PubMed  PubMed Central  CAS  Google Scholar 

  • Bruunsgaard H, Andersen-Ranberg K, Hjelmborg JB, Pedersen BK, Jeune B (2003a) Elevated levels of tumor necrosis factor alpha and mortality in centenarians. Am J Med 115:278–283

    PubMed  CAS  Google Scholar 

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

    PubMed  PubMed Central  CAS  Google Scholar 

  • Bryl E, Vallejo AN, Matteson EL, Witkowski JM, Weyand CM, Goronzy JJ (2005) Modulation of CD28 expression with anti-tumor necrosis factor alpha therapy in rheumatoid arthritis. Arthritis Rheum 52:2996–3003

    PubMed  CAS  Google Scholar 

  • Calado RT, Young NS (2009) Telomere diseases. N Engl J Med 361:2353–2365

    PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    PubMed  Google Scholar 

  • Carrel AL, McVean JJ, Clark RR, Peterson SE, Eickhoff JC, Allen DB (2009) School-based exercise improves fitness, body composition, insulin sensitivity, and markers of inflammation in non-obese children. J Pediatr Endocrinol Metab 22:409–415

    PubMed  Google Scholar 

  • Cawthon RM, Smith KR, O’Brien E, Sivatchenko A, Kerber RA (2003) Association between telomere length in blood and mortality in people aged 60 years or older. Lancet 361:393–395

    PubMed  CAS  Google Scholar 

  • Centres for Disease Control and Prevention. Seasonal influenza (flu). Available at: http:www.cdc.gov/flu/about/qa/disease.htm Accessed 15 April 2010. Ref Type: Internet Communication

  • Chung ES, Packer M, Lo KH, Fasanmade AA, Willerson JT (2003) Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial. Circulation 107:3133–3140

    PubMed  CAS  Google Scholar 

  • Chung HY, Sung B, Jung KJ, Zou Y, Yu BP (2006) The molecular inflammatory process in aging. Antioxid Redox Signal 8:572–581

    PubMed  CAS  Google Scholar 

  • Chung CP, Oeser A, Solus JF, Avalos I, Gebretsadik T, Shintani A, Raggi P, Sokka T, Pincus T, Stein CM (2008) Prevalence of the metabolic syndrome is increased in rheumatoid arthritis and is associated with coronary atherosclerosis. Atherosclerosis 196:756–763

    PubMed  CAS  Google Scholar 

  • Chung HY, Cesari M, Anton S, Marzetti E, Giovannini S, Seo AY, Carter C, Yu BP, Leeuwenburgh C (2009) Molecular inflammation: underpinnings of aging and age-related diseases. Ageing Res Rev 8:18–30

    PubMed  PubMed Central  CAS  Google Scholar 

  • Cohen HJ, Pieper CF, Harris T, Rao KM, Currie MS (1997) The association of plasma IL-6 levels with functional disability in community-dwelling elderly. J Gerontol A Biol Sci Med Sci 52:M201–M208

    PubMed  CAS  Google Scholar 

  • Cohen AD, Sherf M, Vidavsky L, Vardy DA, Shapiro J, Meyerovitch J (2008) Association between psoriasis and the metabolic syndrome. A cross-sectional study. Dermatology 216:152–155

    PubMed  CAS  Google Scholar 

  • Debigare R, Cote CH, Maltais F (2001) Peripheral muscle wasting in chronic obstructive pulmonary disease. Clinical relevance and mechanisms. Am J Respir Crit Care Med 164:1712–1717

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Dewys WD, Begg C, Lavin PT, Band PR, Bennett JM, Bertino JR, Cohen MH, Douglass HO Jr, Engstrom PF, Ezdinli EZ, Horton J, Johnson GJ, Moertel CG, Oken MM, Perlia C, Rosenbaum C, Silverstein MN, Skeel RT, Sponzo RW, Tormey DC (1980) Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. Am J Med 69:491–497

    PubMed  CAS  Google Scholar 

  • Di Mitri D, Azevedo RI, Henson SM, Libri V, Riddell NE, Macaulay R, Kipling D, Soares MV, Battistini L, Akbar AN (2011) Reversible senescence in human CD4+CD45RA+. J Immunol 187:2093–2100

    PubMed  Google Scholar 

  • Dinarello CA (2011) Blocking interleukin-1beta in acute and chronic autoinflammatory diseases. J Intern Med 269:16–28

    PubMed  PubMed Central  CAS  Google Scholar 

  • Dodeller F, Skapenko A, Kalden JR, Lipsky PE, Schulze-Koops H (2005) The p38 mitogen-activated protein kinase regulates effector functions of primary human CD4 T cells. Eur J Immunol 35:3631–3642

    PubMed  CAS  Google Scholar 

  • Dunne PJ, Belaramani L, Fletcher JM, Fernandez DM, Lawrenz M, Soares MV, Rustin MH, Lam EW, Salmon M, Akbar AN (2005) Quiescence and functional reprogramming of Epstein–Barr virus (EBV)-specific CD8+ T cells during persistent infection. Blood 106:558–565

    PubMed  CAS  Google Scholar 

  • El Ani D, Zimlichman R, Mashiach Y, Shainberg A (2007) Adenosine and TNF-alpha exert similar inotropic effect on heart cultures, suggesting a cardioprotective mechanism against hypoxia. Life Sci 81:803–813

    PubMed  CAS  Google Scholar 

  • Ershler WB (2007) A gripping reality: oxidative stress, inflammation, and the pathway to frailty. J Appl Physiol 103:3–5

    PubMed  CAS  Google Scholar 

  • Feldmann M, Maini RN (2003) Lasker Clinical Medical Research Award. TNF defined as a therapeutic target for rheumatoid arthritis and other autoimmune diseases. Nat Med 9:1245–1250

    PubMed  CAS  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 

  • Fontana L (2009) Neuroendocrine factors in the regulation of inflammation: excessive adiposity and calorie restriction. Exp Gerontol 44:41–45

    PubMed  PubMed Central  CAS  Google Scholar 

  • Forsythe LK, Wallace JM, Livingstone MB (2008) Obesity and inflammation: the effects of weight loss. Nutr Res Rev 21:117–133

    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 N Y Acad Sci 908:244–254

    PubMed  CAS  Google Scholar 

  • Franceschi C, Capri M, Monti D, Giunta S, Olivieri F, Sevini F, Panourgia MP, Invidia L, Celani L, Scurti M, Cevenini E, Castellani GC, Salvioli S (2007) Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev 128:92–105

    PubMed  CAS  Google Scholar 

  • Freeman RB Jr (2009) The ‘indirect’ effects of cytomegalovirus infection. Am J Transplant 9:2453–2458

    PubMed  CAS  Google Scholar 

  • Geist LJ, Hopkins HA, Dai LY, He B, Monick MM, Hunninghake GW (1997) Cytomegalovirus modulates transcription factors necessary for the activation of the tumor necrosis factor-alpha promoter. Am J Respir Cell Mol Biol 16:31–37

    PubMed  CAS  Google Scholar 

  • Ghanim H, Sia CL, Abuaysheh S, Korzeniewski K, Patnaik P, Marumganti A, Chaudhuri A, Dandona P (2010) An antiinflammatory and reactive oxygen species suppressive effects of an extract of Polygonum cuspidatum containing resveratrol. J Clin Endocrinol Metab 95:E1–E8

    PubMed  PubMed Central  Google Scholar 

  • Giunta S (2008) Exploring the complex relations between inflammation and aging (inflamm-aging): anti-inflamm-aging remodelling of inflamm-aging, from robustness to frailty. Inflamm Res 57:558–563

    PubMed  CAS  Google Scholar 

  • Gomez CR, Acuna-Castillo C, Nishimura S, Perez V, Escobar A, Salazar-Onfray F, Sabaj V, Torres C, Walter R, Sierra F (2006) Serum from aged F344 rats conditions the activation of young macrophages. Mech Ageing Dev 127:257–263

    PubMed  CAS  Google Scholar 

  • Gonzalez O, Tobia C, Ebersole J, Novak M (2011) Caloric restriction and chronic inflammatory diseases. Oral Dis 18:16–31

    PubMed  PubMed Central  Google Scholar 

  • Gonzalez-Gay MA, Gonzalez-Juanatey C, Vazquez-Rodriguez TR, Miranda-Filloy JA, Llorca J (2010) Insulin resistance in rheumatoid arthritis: the impact of the anti-TNF-alpha therapy. Ann N Y Acad Sci 1193:153–159

    PubMed  CAS  Google Scholar 

  • Goodwin K, Viboud C, Simonsen L (2006) Antibody response to influenza vaccination in the elderly: a quantitative review. Vaccine 24:1159–1169

    PubMed  CAS  Google Scholar 

  • Gorczynski RM, Terzioglu E (2008) Aging and the immune system. Int Urol Nephrol 40:1117–1125

    PubMed  Google Scholar 

  • Goronzy JJ, Shao L, Weyand CM (2010) Immune aging and rheumatoid arthritis. Rheum Dis Clin North Am 36:297–310

    PubMed  PubMed Central  Google Scholar 

  • Gouin JP, Hantsoo L, Kiecolt-Glaser JK (2008) Immune dysregulation and chronic stress among older adults: a review. Neuroimmunomodulation 15:251–259

    PubMed  PubMed Central  CAS  Google Scholar 

  • Grivennikov SI, Karin M (2011) Inflammatory cytokines in cancer: tumour necrosis factor and interleukin 6 take the stage. Ann Rheum Dis 70(Suppl 1):i104–i108

    PubMed  CAS  Google Scholar 

  • Gupta S, Bi R, Kim C, Chiplunkar S, Yel L, Gollapudi S (2005) Role of NF-kappaB signaling pathway in increased tumor necrosis factor-alpha-induced apoptosis of lymphocytes in aged humans. Cell Death Differ 12:177–183

    PubMed  CAS  Google Scholar 

  • Gupta S, Su H, Bi R, Gollapudi S (2006) Differential sensitivity of naive and memory subsets of human CD8+ T cells to TNF-alpha-induced apoptosis. J Clin Immunol 26:193–203

    PubMed  CAS  Google Scholar 

  • Haynes L, Eaton SM (2005) The effect of age on the cognate function of CD4+ T cells. Immunol Rev 205:220–228

    PubMed  PubMed Central  CAS  Google Scholar 

  • Haynes L, Eaton SM, Swain SL (2000) The defects in effector generation associated with aging can be reversed by addition of IL-2 but not other related gamma(c)-receptor binding cytokines. Vaccine 18:1649–1653

    PubMed  CAS  Google Scholar 

  • Heilbronn LK, de Jonge L, Frisard MI, DeLany JP, Larson-Meyer DE, Rood J, Nguyen T, Martin CK, Volaufova J, Most MM, Greenway FL, Smith SR, Deutsch WA, Williamson DA, Ravussin E (2006) Effect of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals: a randomized controlled trial. JAMA 295:1539–1548

    PubMed  PubMed Central  CAS  Google Scholar 

  • Ho JE, Hsue PY (2009) Cardiovascular manifestations of HIV infection. Heart 95:1193–1202

    PubMed  Google Scholar 

  • Ingram DK, Anson RM, de Cabo R, Mamczarz J, Zhu M, Mattison J, Lane MA, Roth GS (2004) Development of calorie restriction mimetics as a prolongevity strategy. Ann N Y Acad Sci 1019:412–423

    PubMed  CAS  Google Scholar 

  • Jolly CA (2004) Dietary restriction and immune function. J Nutr 134:1853–1856

    PubMed  CAS  Google Scholar 

  • Kebschull M, Demmer RT, Papapanou PN (2010) “Gum bug, leave my heart alone!”—epidemiologic and mechanistic evidence linking periodontal infections and atherosclerosis. J Dent Res 89:879–902

    PubMed  PubMed Central  CAS  Google Scholar 

  • Kim HJ, Jung KJ, Yu BP, Cho CG, Choi JS, Chung HY (2002) Modulation of redox-sensitive transcription factors by calorie restriction during aging. Mech Ageing Dev 123:1589–1595

    PubMed  CAS  Google Scholar 

  • Kim DH, Kim JY, Yu BP, Chung HY (2008) The activation of NF-kappaB through Akt-induced FOXO1 phosphorylation during aging and its modulation by calorie restriction. Biogerontology 9:33–47

    PubMed  CAS  Google Scholar 

  • Kops GJ, Dansen TB, Polderman PE, Saarloos I, Wirtz KW, Coffer PJ, Huang TT, Bos JL, Medema RH, Burgering BM (2002) Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress. Nature 419:316–321

    PubMed  CAS  Google Scholar 

  • Larbi A, Pawelec G, Wong SC, Goldeck D, Tai JJ, Fulop T (2011) Impact of age on T cell signaling: a general defect or specific alterations? Ageing Res Rev 10:370–378

    PubMed  CAS  Google Scholar 

  • Lavallee P, Perchaud V, Gautier-Bertrand M, Grabli D, Amarenco P (2002) Association between influenza vaccination and reduced risk of brain infarction. Stroke 33:513–518

    PubMed  Google Scholar 

  • Lencel P, Magne D (2011) Inflammaging: the driving force in osteoporosis? Med Hypotheses 76:317–321

    PubMed  CAS  Google Scholar 

  • Li C, Beavis P, Palfreeman AC, Amjadi P, Kennedy A, Brennan FM (2011a) Activation of p38 mitogen-activated protein kinase is critical step for acquisition of effector function in cytokine-activated T cells, but acts as a negative regulator in T cells activated through the T-cell receptor. Immunology 132:104–110

    PubMed  PubMed Central  CAS  Google Scholar 

  • Li H, Yan Z, Zhu J, Yang J, He J (2011b) Neuroprotective effects of resveratrol on ischemic injury mediated by improving brain energy metabolism and alleviating oxidative stress in rats. Neuropharmacology 60:252–258

    PubMed  CAS  Google Scholar 

  • Li Q, Verma IM (2002) NF-kappaB regulation in the immune system. Nat Rev Immunol 2:725–734

    Google Scholar 

  • Libby P, Okamoto Y, Rocha VZ, Folco E (2010) Inflammation in atherosclerosis: transition from theory to practice. Circ J 74:213–220

    PubMed  CAS  Google Scholar 

  • Licastro F, Candore G, Lio D, Porcellini E, Colonna-Romano G, Franceschi C, Caruso C (2005) Innate immunity and inflammation in ageing: a key for understanding age-related diseases. Immun Ageing 2:8

    PubMed  PubMed Central  Google Scholar 

  • Maggio M, Basaria S, Ble A, Lauretani F, Bandinelli S, Ceda GP, Valenti G, Ling SM, Ferrucci L (2006) Correlation between testosterone and the inflammatory marker soluble interleukin-6 receptor in older men. J Clin Endocrinol Metab 91:345–347

    PubMed  CAS  Google Scholar 

  • Mann DL, McMurray JJ, Packer M, Swedberg K, Borer JS, Colucci WS, Djian J, Drexler H, Feldman A, Kober L, Krum H, Liu P, Nieminen M, Tavazzi L, van Veldhuisen DJ, Waldenstrom A, Warren M, Westheim A, Zannad F, Fleming T (2004) Targeted anticytokine therapy in patients with chronic heart failure: results of the Randomized Etanercept Worldwide Evaluation (RENEWAL). Circulation 109:1594–1602

    PubMed  CAS  Google Scholar 

  • Merritt C, Enslen H, Diehl N, Conze D, Davis RJ, Rincon M (2000) Activation of p38 mitogen-activated protein kinase in vivo selectively induces apoptosis of CD8(+) but not CD4(+) T cells. Mol Cell Biol 20:936–946

    PubMed  PubMed Central  CAS  Google Scholar 

  • Messaoudi I, Fischer M, Warner J, Park B, Mattison J, Ingram DK, Totonchy T, Mori M, Nikolich-Zugich J (2008) Optimal window of caloric restriction onset limits its beneficial impact on T-cell senescence in primates. Aging Cell 7:908–919

    PubMed  PubMed Central  CAS  Google Scholar 

  • Monteiro R, Azevedo I (2010) Chronic inflammation in obesity and the metabolic syndrome. Mediators Inflamm doi:10.1155/2010/289645

  • Morales I, Farias G, Maccioni RB (2010) Neuroimmunomodulation in the pathogenesis of Alzheimer’s disease. Neuroimmunomodulation 17:202–204

    PubMed  CAS  Google Scholar 

  • Morley JE, Baumgartner RN, Roubenoff R, Mayer J, Nair KS (2001) Sarcopenia. J Lab Clin Med 137:231–243

    PubMed  CAS  Google Scholar 

  • Naghavi M, Wyde P, Litovsky S, Madjid M, Akhtar A, Naguib S, Siadaty MS, Sanati S, Casscells W (2003) Influenza infection exerts prominent inflammatory and thrombotic effects on the atherosclerotic plaques of apolipoprotein E-deficient mice. Circulation 107:762–768

    PubMed  CAS  Google Scholar 

  • Nayak BN, Friel JK, Rempel CB, Jones PJ (2009) Energy-restricted diets result in higher numbers of CD4+, CD8+, immunoglobulins (A, M, and G), and CD45RA cells in spleen and CD4+, immunoglobulin A, and CD45RA cells in colonic lamina propria of rats. Nutr Res 29:487–493

    PubMed  CAS  Google Scholar 

  • Parish ST, Wu JE, Effros RB (2009) Modulation of T lymphocyte replicative senescence via TNF-{alpha} inhibition: role of caspase-3. J Immunol 182:4237–4243

    PubMed  PubMed Central  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Pearson KJ, Baur JA, Lewis KN, Peshkin L, Price NL, Labinskyy N, Swindell WR, Kamara D, Minor RK, Perez E, Jamieson HA, Zhang Y, Dunn SR, Sharma K, Pleshko N, Woollett LA, Csiszar A, Ikeno Y, Le Couteur D, Elliott PJ, Becker KG, Navas P, Ingram DK, Wolf NS, Ungvari Z, Sinclair DA, de Cabo R (2008) Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab 8:157–168

    PubMed  PubMed Central  CAS  Google Scholar 

  • Phrommintikul A, Kuanprasert S, Wongcharoen W, Kanjanavanit R, Chaiwarith R, Sukonthasarn A (2011) Influenza vaccination reduces cardiovascular events in patients with acute coronary syndrome. Eur Heart J. 32: 1730–1735

    Google Scholar 

  • Qiu H, Straat K, Rahbar A, Wan M, Soderberg-Naucler C, Haeggstrom JZ (2008) Human CMV infection induces 5-lipoxygenase expression and leukotriene B4 production in vascular smooth muscle cells. J Exp Med 205:19–24

    PubMed  PubMed Central  CAS  Google Scholar 

  • Reed JR, Vukmanovic-Stejic M, Fletcher JM, Soares MV, Cook JE, Orteu CH, Jackson SE, Birch KE, Foster GR, Salmon M, Beverley PC, Rustin MH, Akbar AN (2004) Telomere erosion in memory T cells induced by telomerase inhibition at the site of antigenic challenge in vivo. J Exp Med 199:1433–1443

    PubMed  PubMed Central  CAS  Google Scholar 

  • Rincon M, Pedraza-Alva G (2003) JNK and p38 MAP kinases in CD4+ and CD8+ T cells. Immunol Rev 192:131–142

    PubMed  CAS  Google Scholar 

  • Riou C, Yassine-Diab B, Van Grevenynghe J, Somogyi R, Greller LD, Gagnon D, Gimmig S, Wilkinson P, Shi Y, Cameron MJ, Campos-Gonzalez R, Balderas RS, Kelvin D, Sekaly RP, Haddad EK (2007) Convergence of TCR and cytokine signaling leads to FOXO3a phosphorylation and drives the survival of CD4+ central memory T cells. J Exp Med 204:79–91

    PubMed  PubMed Central  CAS  Google Scholar 

  • Rossi JF, Negrier S, James ND, Kocak I, Hawkins R, Davis H, Prabhakar U, Qin X, Mulders P, Berns B (2010) A phase I/II study of siltuximab (CNTO 328), an anti-interleukin-6 monoclonal antibody, in metastatic renal cell cancer. Br J Cancer 103:1154–1162

    PubMed  PubMed Central  CAS  Google Scholar 

  • Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, Meade TW (2011) Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet 377:31–41

    PubMed  CAS  Google Scholar 

  • Ruder EH, Laiyemo AO, Graubard BI, Hollenbeck AR, Schatzkin A, Cross AJ (2011) Non-steroidal anti-inflammatory drugs and colorectal cancer risk in a large, prospective cohort. Am J Gastroenterol 106:1340–1350

    PubMed  PubMed Central  CAS  Google Scholar 

  • Schafer PH, Wang L, Wadsworth SA, Davis JE, Siekierka JJ (1999) T cell activation signals up-regulate p38 mitogen-activated protein kinase activity and induce TNF-alpha production in a manner distinct from LPS activation of monocytes. J Immunol 162:659–668

    PubMed  CAS  Google Scholar 

  • Seriolo B, Paolino S, Sulli A, Ferretti V, Cutolo M (2006) Bone metabolism changes during anti-TNF-alpha therapy in patients with active rheumatoid arthritis. Ann N Y Acad Sci 1069:420–427

    PubMed  CAS  Google Scholar 

  • Sethi JK, Vidal-Puig AJ (2007) Thematic review series: adipocyte biology. Adipose tissue function and plasticity orchestrate nutritional adaptation. J Lipid Res 48:1253–1262

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  PubMed Central  CAS  Google Scholar 

  • Simonsen L, Reichert TA, Viboud C, Blackwelder WC, Taylor RJ, Miller MA (2005) Impact of influenza vaccination on seasonal mortality in the US elderly population. Arch Intern Med 165:265–272

    PubMed  Google Scholar 

  • Siscovick DS, Raghunathan TE, Lin D, Weinmann S, Arbogast P, Lemaitre RN, Psaty BM, Alexander R, Cobb LA (2000) Influenza vaccination and the risk of primary cardiac arrest. Am J Epidemiol 152:674–677

    PubMed  CAS  Google Scholar 

  • Sobieszczyk, ME, Hoover, DR, Anastos, K, Mulligan, K, Tan, T, Shi, Q, Gao, W, Hyman, C, Cohen, MH, Cole, SR, Plankey, MW, Levine, AM, Justman, J (2008) Prevalence and predictors of metabolic syndrome among HIV-infected and HIV-uninfected women in the Women's Interagency HIV Study. J Acquir Immune Defic Syndr. 48:272–280

    Google Scholar 

  • Swindell, WR (2009) Genes and gene expression modules associated with caloric restriction and aging in the laboratory mouse. BMC Genomics. 10:585.

    Google Scholar 

  • Vainas T, Sayed S, Bruggeman CA, Stassen FR (2009) Exploring the role of Chlamydia pneumoniae in cardiovascular disease: a narrative review. Drugs Today 45(Suppl B):165–172

    Google Scholar 

  • van de Berg PJ, van Stijn A, ten Berge IJ, van Lier RA (2008) A fingerprint left by cytomegalovirus infection in the human T cell compartment. J Clin Virol 41:213–217

    PubMed  Google Scholar 

  • van de Berg PJ, Griffiths SJ, Yong SL, Macaulay R, Bemelman FJ, Jackson S, Henson SM, ten Berge IJ, Akbar AN, van Lier RA (2010) Cytomegalovirus infection reduces telomere length of the circulating T cell pool. J Immunol 184:3417–3423

    PubMed  Google Scholar 

  • Van Doornum S, McColl G, Wicks IP (2002) Accelerated atherosclerosis: an extraarticular feature of rheumatoid arthritis? Arthritis Rheum 46:862–873

    PubMed  Google Scholar 

  • Wang CS, Wang ST, Lai CT, Lin LJ, Chou P (2007a) Impact of influenza vaccination on major cause-specific mortality. Vaccine 25:1196–1203

    PubMed  CAS  Google Scholar 

  • Wang Y, Yin B, Liu S, Xue S (2007b) Cardioprotective effect by tumor necrosis factor-alpha and interleukin-6 through late preconditioning in unstable angina patients. Arch Med Res 38:80–85

    PubMed  CAS  Google Scholar 

  • Wanke CA, Silva M, Knox TA, Forrester J, Speigelman D, Gorbach SL (2000) Weight loss and wasting remain common complications in individuals infected with human immunodeficiency virus in the era of highly active antiretroviral therapy. Clin Infect Dis 31:803–805

    PubMed  CAS  Google Scholar 

  • Weinberger B, Lazuardi L, Weiskirchner I, Keller M, Neuner C, Fischer KH, Neuman B, Wurzner R, Grubeck-Loebenstein B (2007) Healthy aging and latent infection with CMV lead to distinct changes in CD8+ and CD4+ T-cell subsets in the elderly. Hum Immunol 68:86–90

    PubMed  CAS  Google Scholar 

  • Wen H, Gris D, Lei Y, Jha S, Zhang L, Huang MT, Brickey WJ, Ting JP (2011) Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling. Nat Immunol 12:408–415

    PubMed  CAS  Google Scholar 

  • Westlake SL, Colebatch AN, Baird J, Curzen N, Kiely P, Quinn M, Choy E, Ostor AJ, Edwards CJ (2011) Tumour necrosis factor antagonists and the risk of cardiovascular disease in patients with rheumatoid arthritis: a systematic literature review. Rheumatology 50:518–531

    CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Williams JG, Jurkovich GJ, Hahnel GB, Maier RV (1992) Macrophage priming by interferon gamma: a selective process with potentially harmful effects. J Leukoc Biol 52:579–584

    PubMed  CAS  Google Scholar 

  • Zhang X, Sun S, Hwang I, Tough DF, Sprent J (1998) Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL-15. Immunity 8:591–599

    PubMed  CAS  Google Scholar 

  • Zhang X, Fujii H, Kishimoto H, LeRoy E, Surh CD, Sprent J (2002) Aging leads to disturbed homeostasis of memory phenotype CD8(+) cells. J Exp Med 195:283–293

    PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgements

The authors wish to acknowledge support from the Medical Research Council (RM), and the British Biotechnology and Biological Sciences Research Council (ANA, SMH).

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Authors and Affiliations

  1. Division of Infection and Immunity, Rayne Institute, University College London, 5 University Street, London, WC1E 6JF, UK

    Richard Macaulay, Arne N. Akbar & Sian M. Henson

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  1. Richard Macaulay
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  2. Arne N. Akbar
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  3. Sian M. Henson
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Corresponding author

Correspondence to Sian M. Henson.

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Authorship

R.M. surveyed the literature and wrote the paper. S.M.H. and A.A. reviewed the manuscript.

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Macaulay, R., Akbar, A.N. & Henson, S.M. The role of the T cell in age-related inflammation. AGE 35, 563–572 (2013). https://doi.org/10.1007/s11357-012-9381-2

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  • DOI: https://doi.org/10.1007/s11357-012-9381-2

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