Role of Lipid Rafts in Activation-Induced Cell Death : The Fas Pathway in Aging

  • Anis Larbi
  • Elisa Muti
  • Roberta Giacconi
  • Eugenio Mocchegiani
  • Tamàs Fülöp
Part of the Advances in Experimental Medicine and Biology book series (volume 584)


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7. References

  1. 1.
    S.W. Hetts, To die or not to die: an overview of apoptosis and its role in disease, JAMA. 279, 300–307 (1998).PubMedCrossRefGoogle Scholar
  2. 2.
    D. Kabelitz, and O. Janssen, Antigen-induced death of T-lymphocytes. Front Biosci. 2, d61–77 (1997).PubMedGoogle Scholar
  3. 3.
    O. Janssen, R. Sanzenbacher, and D. Kabelitz, Regulation of activation-induced cell death of mature T-lymphocyte populations. Cell Tissue Res. 301, 85–99 (2000).PubMedCrossRefGoogle Scholar
  4. 4.
    A. Oehm, I. Behrman, W. Falk, M. Pawlita, G. Maier, C. Klas, M. Li-Weber, S. Richards, J. Dhein, B.C. Trauth, H. Ponsting, and P.H. Krammer, Purification and molecular cloning of the APO-1 cell surface antigen, a member of the tumor necrosis factor/nerve growth factor receptor superfamily. Sequence identity with the Fas antigen. J Biol Chem. 267, 10709–10715 (1992).PubMedGoogle Scholar
  5. 5.
    S. Nagata, and P. Golstein, The Fas death factor. Science. 267, 1449–1456 (1995).PubMedCrossRefGoogle Scholar
  6. 6.
    K. Simons, and E. Ikonen, Functional rafts in cell membranes. Nature. 387, 569–572 (1997).PubMedCrossRefGoogle Scholar
  7. 7.
    D. Scheel-Toellner, K. Wang, R. Singh, S. Majeed, K. Raza, S.J. Curnow, M. Salmon, and J.M. Lord, The death-inducing signalling complex is recruited to lipid rafts in Fasinduced apoptosis. Biochem Biophys Res Commun. 297, 876–879 (2002).PubMedCrossRefGoogle Scholar
  8. 8.
    A. Larbi, N. Douziech, G. Dupuis, A. Khalil, H. Pelletier, K.P. Guérard, and T. Fulop, Age-associated alterations in the recruitment of signal-transduction proteins to lipid rafts in human T lymphocytes. J Leukoc Biol. 75, 373–381 (2004).PubMedCrossRefGoogle Scholar
  9. 9.
    T. Fulop, A. Larbi, G. Dupuis, and G. Pawelec, Ageing, autoimmunity and arthritis: Perturbations of TCR signal transduction pathways with ageing — a biochemical paradigm for the ageing immune system. Arthritis Res Ther. 5, 290–302 (2003).PubMedCrossRefGoogle Scholar
  10. 10.
    A.H. Wyllie, What is apoptosis. Histopathology. 10, 995–998 (1986).PubMedCrossRefGoogle Scholar
  11. 11.
    I.N. Crispe, Death and destruction of activated T lymphocytes. Immunol Res. 19, 143–157 (1999).PubMedGoogle Scholar
  12. 12.
    A.H. Wyllie, R.G. Morris, A.L. Smith, and D.J. Dunlop, Chromatin cleavage in apoptosis: association with condensed chromatin morphology and dependence on macromolecular synthesis J Pathol. 142, 67–77 (1984).PubMedCrossRefGoogle Scholar
  13. 13.
    J. Yang, X. Liu, K. Bhalla, C.N. Kim, A.M. Ibrado, J. Cai, T.I. Peng, D.P. Jones, and X. Wang, Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science. 275, 1129–1132 (1997).PubMedCrossRefGoogle Scholar
  14. 14.
    M. Castedo, T. Hirsch, S.A. Susin, N. Zamzani, P. Marchetti, A. Macho, and G.J. Kroeger, Sequential acquisition of mitochondrial and plasma membrane alterations during early lymphocyte apoptosis J Immunol. 157, 512–521 (1996).PubMedGoogle Scholar
  15. 15.
    A. Walker, C. Ward, E.L. Taylor, I. Dransfield, S.P. Hart, C. Haslett, and A.G. Rossi, Regulation of neutrophil apoptosis and removal of apoptotic cells. Curr Drug Targets Inflamm Allergy. 4, 447–454 (2005).PubMedCrossRefGoogle Scholar
  16. 16.
    L.L. Carter, X. Zhang, C. Dubey, P. Rogers, L. Tsui, and S.L. Swain, Regulation of T cell subsets from naive to memory. J Immunother. 21, 181–187 (1998).PubMedCrossRefGoogle Scholar
  17. 17.
    A.E. Nel, T-cell activation through the antigen receptor. Part 1: signaling components, signaling pathways, and signal integration at the T-cell antigen receptor synapse. J Allergy Clin Immunol. 109, 758–770 (2002).PubMedCrossRefGoogle Scholar
  18. 18.
    S.G. Maher, C.E. Condron, D.J. Bouchier-Hayes, and D.M. Toomey, Taurine attenuates CD3/interleukin-2-induced T cell apoptosis in an in vitro model of activationinduced cell death (AICD). Clin Exp Immunol. 139, 279–286 (2005).PubMedCrossRefGoogle Scholar
  19. 19.
    P.H. Krammer, CD95(APO-1/Fas)-mediated apoptosis: live and let die. Adv Immunol. 71, 163–210 (1997).Google Scholar
  20. 20.
    P. Golstein, Cell death: TRAIL and its receptors. Curr Biol. 7, R750–753 (1997).PubMedCrossRefGoogle Scholar
  21. 21.
    V. Depraetere, and P. Golstein, Fas and other cell death signaling pathways. Semin Immunol. 9, 93–107 (1997).PubMedCrossRefGoogle Scholar
  22. 22.
    H. Loetscher, Y.C. Pan, H.W. Lahm, R. Gentz, M. Brockhaus, H. Tabuchi, and W. Lesskauer, Molecular cloning and expression of the human 55 kd tumor necrosis factor receptor. Cell. 61, 351–359 (1990).PubMedCrossRefGoogle Scholar
  23. 23.
    N. Itoh, S. Yonehara, A. Ishii, M. Yonehara, S. Mizushima, M. Sameshima, A. Hase, Y. Seto, and S. Nagata, The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell. 66, 233–243 (1991).PubMedCrossRefGoogle Scholar
  24. 24.
    S. Nagata, Apoptosis by death factor. Cell. 88, 355–365 (1997).PubMedCrossRefGoogle Scholar
  25. 25.
    L.A. Tartaglia, T.M. Ayres, G.H. Wong, and D.V. Goeddel, A novel domain within the 55 kd. TNF receptor signals cell death. Cell. 74, 845–853 (1993).PubMedCrossRefGoogle Scholar
  26. 26.
    G. Pan, J. Ni, Y.F. Wei, G. Yu, R. Gentz, and V.M. Dixit, An antagonist decoy receptor and a death domain-containing receptor for TRAIL. Science. 277, 815–818 (1997).PubMedCrossRefGoogle Scholar
  27. 27.
    R.N. Kolesnick, A. Haimovitz-Friedman, and Z. Fuks, The sphingomyelin signal transduction pathway mediates apoptosis for tumor necrosis factor, Fas, and ionizing radiation. Biochem Cell Biol. 72, 471–474 (1994).PubMedCrossRefGoogle Scholar
  28. 28.
    W. Stoffel, Functional analysis of acid and neutral sphingomyelinases in vitro and in vivo. Chem Phys Lipids. 102, 107–121 (1999).PubMedCrossRefGoogle Scholar
  29. 29.
    A. Lahm, A. Paradisi, D.R. Green, and G. Melino, Death fold domain interaction in apoptosis. Cell Death Differ. 10, 10–12 (2003).PubMedCrossRefGoogle Scholar
  30. 30.
    S.W. Lee, Y.G. Ko, S. Bang, K.S. Kim, and S. Kim, Death effector domain of a mammalian apoptosis mediator, FADD, induces bacterial cell death. Mol Microbiol. 35, 1540–1549 (2000).PubMedCrossRefGoogle Scholar
  31. 31.
    T. Van den Berghe, G. van Loo, X. Saelens, M. van Gurp, G. Brouckaert, M. Kalai, W. Declerq, and P.J. Vandenabeele, Differential signaling to apoptotic and necrotic cell death by Fas-associated death domain protein FADD. J. Biol Chem. 279, 7925–7933 (2004).CrossRefGoogle Scholar
  32. 32.
    J.P. Medema, R.E. Toes, C. Scaffidi, T.S. Zheng, R.A. Flavell, C.J. Melief, M.E. Peter, R. Offringa, and P.H. Krammer, Cleavage of FLICE (caspase-8) by granzyme B during cytotoxic T lymphocyte-induced apoptosis. Eur J Immunol. 27, 3492–3498 (1997).PubMedGoogle Scholar
  33. 33.
    H. Hirata, A. Takahashi, S. Kobayashi, S. Yonehara, H. Sawai, T. Okazaki, K. Yamamoto, and M. Sasada, Caspases are activated in a branched protease cascade and control distinct downstream processes in Fas-induced apoptosis. J Exp Med. 187, 587–600 (1998).PubMedCrossRefGoogle Scholar
  34. 34.
    N. Yasuda, K. Gotoh, S. Minatoguchi, K. Asano, K. Nishigaki, M. Nomura, A. Ohno, M. Watanabe, H. Sano, H. Kumada, T. Sawa, and H. Fujiwara, An increase of soluble Fas, an inhibitor of apoptosis, associated with progression of COPD. Respir Med. 92, 993–999 (1998).PubMedCrossRefGoogle Scholar
  35. 35.
    G. Melzani, G. Bugari, G. Parrinello, G. Mori, A.M. Manganoni, and G. De Panfilis, Evaluation of soluble Fas ligand as a serological marker for melanoma. Dermatology. 205, 111–115 (2002).PubMedCrossRefGoogle Scholar
  36. 36.
    F. Silvestris, D. Grinello, M. Tucci, P. Cafforio, and F. Dammacco, Enhancement of T cell apoptosis correlates with increased serum levels of soluble Fas (CD95/Apo-1) in active lupus. Lupus 12, 8–14 (2003).PubMedCrossRefGoogle Scholar
  37. 37.
    M. Tanaka, T. Itai, M. Adachi, and S. Nagata, Downregulation of Fas ligand by shedding. Nat Med. 4, 31–36 (1998).PubMedCrossRefGoogle Scholar
  38. 38.
    V. Screpanti, R.P. Wallin, H.G. Ljunggren, and A.J. Grandien, A central role for death receptor-mediated apoptosis in the rejection of tumors by NK cells. J Immunol. 167, 2068–2073 (2001).PubMedGoogle Scholar
  39. 39.
    D. Cefai, R. Schwaninger, M. Balli, T. Brunner, and C.D. Gimmi, Functional characterization of Fas ligand on tumor cells escaping active specific immunotherapy. Cell Death Differ. 8, 687–695 (2001).PubMedCrossRefGoogle Scholar
  40. 40.
    J. Dhein, H. Walczak, C. Baumler, K.M. Debatin, and P.H. Krammer, Autocrine Tcell suicide mediated by APO-1/(Fas/CD95). Nature. 373, 438–441 (1995).PubMedCrossRefGoogle Scholar
  41. 41.
    T. Brunner, R.J. Mogil, D. LaFace, N.J. Yoo, A. Mahboubi, F. Echeverri, S.J. Martin, W.R. Force, D.H. Lynch, C.F. Ware, and D.R. Green, Cell-autonomous Fas (CD95)/Fas-ligand interaction mediates activation-induced apoptosis in T-cell hybridomas Nature. 373, 441–444 (1995).PubMedCrossRefGoogle Scholar
  42. 42.
    T.Y. Wang, R. Leventis, and J.R. Silvius, Fluorescence-based evaluation of the partitioning of lipids and lipidated peptides into liquid-ordered lipid microdomains: a model for molecular partitioning into “lipid rafts”. Biophys J. 79, 919–933 (2000).PubMedGoogle Scholar
  43. 43.
    V. Horejsi, The roles of membrane microdomains (rafts) in T cell activation. Immunol Rev. 191:148–164 (2003).PubMedCrossRefGoogle Scholar
  44. 44.
    V. Horejsi, Lipid rafts and their roles in T-cell activation. Microbes Infect. 7:310–316 (2005).PubMedCrossRefGoogle Scholar
  45. 45.
    A. Viola, S. Schroeder, Y. Sakakibara, and A. Lanzavecchia, T lymphocyte costimulation mediated by reorganization of membrane microdomains. Science. 283, 680–682 (1999).PubMedCrossRefGoogle Scholar
  46. 46.
    A. Lanzavecchia, G. Lezzi, and A. Viola, From TCR engagement to T cell activation: a kinetic view of T cell behaviour. Cell. 9, 1–4 (1999).CrossRefGoogle Scholar
  47. 47.
    A.H. Guse, Ca2+ signaling in T-lymphocytes. Crit. Rev. Immunol. 18, 419–448 (1998).PubMedGoogle Scholar
  48. 48.
    S.F. Walk, M.E. March, and K.S. Ravichandran, Roles of Lck, Syk and ZAP-70 tyrosine kinases in TCR-mediated phosphorylation of the adapter protein Shc. Eur. J. Immunol. 28, 2265–2275 (1998).PubMedCrossRefGoogle Scholar
  49. 49.
    R. Bosselut, W.G. Zhang, J.M. Ashe, J.L. Kopacz, L.E. Samelson, and A. Singer, Association of the adaptor molecule LAT with CD4 and CD8 coreceptors identifies a new coreceptor function in T cell receptor signal transduction. J. Exp. Med. 190, 1517–1526 (1999).PubMedCrossRefGoogle Scholar
  50. 50.
    L.P. Kane, J. Lin, and A. Weiss, Signal transduction by the TCR for antigen. Curr. Opin. Immunol. 12, 242–249 (2000).PubMedCrossRefGoogle Scholar
  51. 51.
    A.D. Wells, H. Gudmundsdottir, and L.A. Turka, Following the fate of individuals T cells throughout activation and clonal expansion-signals from T cell receptor and CD28 differentially regulate the induction and duration of a proliferative reponse. J. Clin. Invest. 100, 3173–3183 (1997).PubMedCrossRefGoogle Scholar
  52. 52.
    P. Drevot, C. Langlet, X.J. Guo, A.M. Bernard, O. Colard, J.P. Chauvin, R. Laserre, and H.T. He, TCR signal initiation machinery is pre-assembled and activated in a subset of membrane rafts. EMBO J. 21, 1899–1909 (2002).PubMedCrossRefGoogle Scholar
  53. 53.
    L. Bini, S. Pacini, S. Liberatore, S. Valensin, M. Pellegrini, R. Raggiaschi, V. Pallini, and C.T. Baldari, Extensive temporally regulated reorganization of the lipid raft proteome following T cell antigen receptor triggering. Biochem. J. 369, 301–309 (2003).PubMedCrossRefGoogle Scholar
  54. 54.
    J.A. Rotolo, J. Zhang, M. Donepudi, H. Lee, Z. Fuks, and R.J. Kolesnick, Caspasedependent and-independent activation of acid sphingomyelinase signaling. J Biol Chem. 280, 26425–26434 (2005).PubMedCrossRefGoogle Scholar
  55. 55.
    H. Grassme, A. Jekle, A. Riehle, H. Schwrz, J. Berger, K. Sandhoff, R. Kolesnick, and E.J. Gulbins, CD95 signaling via ceramide-rich membrane rafts. J Biol Chem. 276, 20589–20596 (2001).PubMedCrossRefGoogle Scholar
  56. 56.
    Y. Lavie, and M. Liscovitch, Changes in lipid and protein constituents of rafts and caveolae in multidrug resistant cancer cells and their functional consequences. Glycoconj J. 17, 253–259 (2000).PubMedCrossRefGoogle Scholar
  57. 57.
    V. Ayllon, A. Fleischer, X. Cayla, A. Garcia, and A.J. Rebollo, Segregation of Bad from lipid rafts is implicated in the induction of apoptosis. J Immunol. 168, 3387–3393 (2002).PubMedGoogle Scholar
  58. 58.
    L.A. O’Reilly, U. Divisekera, K. Newton, K. Scalzo, T. Kataoka, H. Puthalakath, M. Ito, D.C. Huang, and A. Strasser, Modifications and intracellular trafficking of FADD/MORT1 and caspase-8 after stimulation of T lymphocytes. Cell Death Differ. 11, 724–736 (2004).PubMedCrossRefGoogle Scholar
  59. 59.
    D.F. Legler, O. Micheau, M.A. Doucey, J. Tschopp, and C. Bron, Recruitment of TNF receptor 1 to lipid rafts is essential for TNFalpha-mediated NF-kappaB activation. Immunity. 18, 655–664 (2003).PubMedCrossRefGoogle Scholar
  60. 60.
    D. Delmas, C. Rebe, O. Micheau, A. Athias, P. Gambert, S. Grazide, G. Laurent, N. Latruffe, and E. Solary, Redistribution of CD95, DR4 and DR5 in rafts accounts for the synergistic toxicity of resveratrol and death receptor ligands in colon carcinoma cells. Oncogene. 23, 8979–8986 (2004).PubMedCrossRefGoogle Scholar
  61. 61.
    D. Delmas, C. Rebe, S. Lacour, R. Filomenko, A. Athias, P. Gambert, M. Cherkaoui-Malki, B. Jannin, L. Dubrez-Daloz, N. Latruffe, and E.J. Solary, Resveratrol-induced apoptosis is associated with Fas redistribution in the rafts and the formation of a death-inducing signaling complex in colon cancer cells J Biol Chem. 278, 41482–41490 (2003).PubMedCrossRefGoogle Scholar
  62. 62.
    J.R. Muppidi, and R.M. Siegel, Ligand-independent redistribution of Fas (CD95) into lipid rafts mediates clonotypic T cell death. Nat Immunol. 5, 182–189 (2004).PubMedCrossRefGoogle Scholar
  63. 63.
    S.M. Aouad, L.Y. Cohen, E. Sharif-Askari, E.K. Haddad, A. Alam, and R.P. Sekaly, Caspase-3 is a component of Fas death-inducing signaling complex in lipid rafts and its activity is required for complete caspase-8 activation during Fas-mediated cell death. J Immunol. 172, 2316–2323 (2004).PubMedGoogle Scholar
  64. 64.
    A. Garcia, X. Cayla, A. Fleischer, J. Guergnon, F. Alvarez-Franco Canas, M.P. Rebollo, F. Roncal, and A. Rebollo, Rafts: a simple way to control apoptosis by subcellular redistribution. Biochimie. 85, 727–731 (2003).PubMedCrossRefGoogle Scholar
  65. 65.
    A. Larbi, N. Douziech, A. Khalil, G. Dupuis, S. Gherairi, K.P. Guerard, and T. Fulop, Effects of methyl-beta-cyclodextrin on T lymphocytes lipid rafts with aging. Exp Gerontol. 39, 551–558 (2004).PubMedCrossRefGoogle Scholar
  66. 66.
    R. Gniadecki, Depletion of membrane cholesterol causes ligand-independent activation of Fas and apoptosis. Biochem Biophys Res Commun. 320, 165–169 (2004).PubMedCrossRefGoogle Scholar
  67. 67.
    J.R. Muppidi, J. Tschopp, and R.M. Siegel, Life and death decisions: secondary complexes and lipid rafts in TNF receptor family signal transduction Immunity. 21, 461–465 (2004).PubMedCrossRefGoogle Scholar
  68. 68.
    D. Scheel-Toellner, K. Wang, L.K. Assi, P.R. Webb, R.M. Craddock, M. Salmon, and J.M. Lord, Clustering of death receptors in lipid rafts initiates neutrophil spontaneous apoptosis. Biochem Soc Trans. 32, 679–681 (2004).PubMedCrossRefGoogle Scholar
  69. 69.
    C. Gajate, and F.J. Mollinedo, Cytoskeleton-mediated death receptor and ligand concentration in lipid rafts forms apoptosis-promoting clusters in cancer chemotherapy. J Biol Chem. 280, 11641–11647 (2005).PubMedCrossRefGoogle Scholar
  70. 70.
    F. Henkler, E. Behrle, K.M. Bennehy, A. Wicovsky, N. Peters, C. Warnke, K. Pfizenmaier, and H. Wajant, The extracellular domains of FasL and Fas are sufficient for the formation of supramolecular FasL-Fas clusters of high stability. J Cell Biol. 168, 1087–1098 (2005).PubMedCrossRefGoogle Scholar
  71. 71.
    T. Fulop, A. Larbi, A. Wikby, E. Mocchegiani, K. Hirokawa, and G. Pawelec, Dysregulation of T-cell function in the elderly: scientific basis and clinical implications. Drugs Aging. 22, 589–603 (2005).PubMedCrossRefGoogle Scholar
  72. 72.
    A. Larbi, N. Douziech, C. Fortin, A. Linteau, G. Dupuis, and T. Fulop, The role of the MAPK pathway alterations in GM-CSF modulated human neutrophil apoptosis with aging. Immun Ageing. 2, 6 (2005).PubMedCrossRefGoogle Scholar
  73. 73.
    C.R. Gomez, E.D. Boehmer, and E.J. Kovacs, The aging innate immune system. Curr Opin Immunol. 17, 457–462 (2005).PubMedCrossRefGoogle Scholar
  74. 74.
    R. Solana, and E. Mariani, NK and NK/T cells in human senescence. Vaccine. 18, 1613–1620 (2000).PubMedCrossRefGoogle Scholar
  75. 75.
    D.D. Taub, and D.L. Longo, Insights into thymic aging and regeneration. Immunol Rev. 205, 72–93 (2005).PubMedCrossRefGoogle Scholar
  76. 76.
    L. Ginaldi, M. De Martinis, D. Monti, and C. Franceschi, The immune system in the elderly: activation-induced and damage-induced apoptosis. Immunol Res. 30, 81–94 (2004).PubMedCrossRefGoogle Scholar
  77. 77.
    J. Pido-Lopez, N. Imami, D. Andrew, and R. Aspinall, Molecular quantitation of thymic output in mice and the effect of IL-7. Eur J Immunol. 32, 2827–2836 (2002).PubMedCrossRefGoogle Scholar
  78. 78.
    J.M. Lord, A.N. Akbar, and D. Kipling, Telomere-based therapy for immunosenescence. Trends Immunol. 23, 175–176 (2002).PubMedCrossRefGoogle Scholar
  79. 79.
    C. Franceschi, S. Valensin, F. Fagnoni, C. Barbi, and M. Bonafe, Biomarkers of immunosenescence within an evolutionary perspective: the challenge of heterogeneity and the role of antigenic load. Exp Gerontol. 34, 911–912 (1999).PubMedCrossRefGoogle Scholar
  80. 80.
    N. Douziech, I. Seres, A. Larbi, E. Szikszay, P.M. Roy, M. Arcand, G., Dupuis, and T. Fulop, Modulation of human lymphocyte proliferative response with aging. Exp Gerontol. 37, 369–387 (2002).PubMedCrossRefGoogle Scholar
  81. 81.
    G. Pawelec, A. Akbar, C. Caruso, R. Solana, B. Grubeck-Loebenstein, and A. Wikby, Human immunosenescence: is it infectious? Immunol Rev. 205, 257–268 (2005).PubMedCrossRefGoogle Scholar
  82. 82.
    G. Pawelec, K. Hirokawa, and T. Fulop, Altered T cell signalling in ageing. Mech Ageing Dev. 122, 1613–1637 (2001).PubMedCrossRefGoogle Scholar
  83. 83.
    G.G. Garcia, and R.A. Miller, Single-cell analyses reveal two defects in peptidespecific activation of naive T cells from aged mice. J Immunol. 166, 3151–3157 (2001).PubMedGoogle Scholar
  84. 84.
    G.G. Garcia, S.B. Berger, A.A. Sadighi Akha, and R.A. Miller, Age-associated changes in glycosylation of CD43 and CD45 on mouse CD4 T cells. Eur J Immunol. 35, 622–631 (2005).PubMedCrossRefGoogle Scholar
  85. 85.
    J.J. Goronzy, and C.M. Weyand, Aging, autoimmunity and arthritis: T-cell senescence and contraction of T-cell repertoire diversity-catalysts of autoimmunity and chronic inflammation. Arthritis Res Ther. 5, 225–234 (2003).PubMedCrossRefGoogle Scholar
  86. 86.
    S. Gupta, H. Su, R. Bi, S. Aggarwal, and S. Gollapudi, Life and death of lymphocytes: a role in immunesenescence. Immun Ageing. 2, 12 (2005).PubMedCrossRefGoogle Scholar
  87. 87.
    S. Aggarwal, and S. Gupta, Increased apoptosis of T cell subsets in aging humans: altered expression of Fas (CD95), Fas ligand, Bcl-2, and Bax. J Immunol. 160, 1627–1637 (1998).PubMedGoogle Scholar
  88. 88.
    S. Gupta, Molecular and biochemical pathways of apoptosis in lymphocytes from aged humans. Vaccine. 18, 1596–1601 (2000).PubMedCrossRefGoogle Scholar
  89. 89.
    S. Aggarwal, and S. Gupta, Increased activity of caspase 3 and caspase 8 in anti-Fasinduced apoptosis in lymphocytes from ageing humans. Clin Exp Immunol. 117, 285–290 (1999).PubMedCrossRefGoogle Scholar
  90. 90.
    C. Spaulding, W. Guo, and R.B. Effros, Resistance to apoptosis in human CD8+ T cells that reach replicative senescence after multiple rounds of antigen-specific proliferation. Exp Gerontol. 34, 633–644 (1999).PubMedCrossRefGoogle Scholar
  91. 91.
    M.A. Phelouzat, A. Arbogast, T. Laforge, R.A. Quadri, and J.J. Proust, Excessive apoptosis of mature T lymphocytes is a characteristic feature of human immune senescence. Mech Ageing Dev. 88, 25–38 (1996).PubMedCrossRefGoogle Scholar
  92. 92.
    D. Monti, S. Salvioli, M. Capri, W. Malorni, E. Straface, A. Cossarizza, B. Botti, M. Piacentini, G. Baggio, C. Barbi, S. Valensin, M. Bonafe, and C. Franceschi, Decreased susceptibility to oxidative stress-induced apoptosis of peripheral blood mononuclear cells from healthy elderly and centenarians. Mech Ageing Dev. 121, 239–250 (2000).PubMedCrossRefGoogle Scholar
  93. 93.
    G. Pawelec, Y. Barnett, R. Forsey, D. Frasca, A. Globerson, J. McLeod, C. Caruso, C. Franceschi, T. Fulop, S. Gupta, E. Mariani, E. Mocchegiani, and R. Solana, T cells and aging, January 2002 update Front Biosci. 7, d1056–1183 (2002).PubMedGoogle Scholar
  94. 94.
    H.C. Hsu, J. Shi, P. Yang, X. Xu, C. Dodd, Y. Matsuki, H.G. Zhang, and J.D. Mountz, Activated CD8(+) T cells from aged mice exhibit decreased activation-induced cell death. Mech Ageing Dev. 122, 1663–1684 (2001).PubMedCrossRefGoogle Scholar
  95. 95.
    T. Yokoyama, J. Du, Y. Kawamoto, H. Suzuki, and I. Nakashima, Inhibition of Fasmediated apoptotic cell death of murine T lymphocytes in a mouse model of immunosenescence in linkage to deterioration in cell membrane raft function. Immunology. 112, 64–71 (2004).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • Anis Larbi
    • 1
  • Elisa Muti
    • 2
  • Roberta Giacconi
    • 2
  • Eugenio Mocchegiani
    • 2
  • Tamàs Fülöp
    • 1
  1. 1.Research Center on Aging, Immunological Graduate Programme, Department of medicine, Department of BiochemistryUniversity of SherbrookeSherbrookeCanada
  2. 2.Research Department INRCASection Nutrition, Immunity and Aging, Immunology CentreAnconaItaly

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