Telomeres, Telomerase and CD28 in Human CD8 T-Cells: Effects on Immunity during Aging and HIV Infection

  • Steven R. Fauce
  • Rita B. Effros
Part of the Medical Intelligence Unit book series (MIUN)


The immune system undergoes major alterations during aging, many of which have been implicated in the increased morbidity and mortality associated with infection, as well as the high incidence of cancer in the elderly. Although mouse models have provided important insights into immunosenescence, there are certain facets of human immunological history that cannot be modeled in experimental animals. Here, we focus on the process of replicative senescence in human CD8 T-cells, which seems to be driven by the extensive and long-term cell proliferation required to control certain latent viral infections. Replicative senescence has been well-characterized in cell culture fand is now recognized as an underlying mechanism for shaping the memory T-cell pool in humans. This chapter will focus on the complex relationship between telomeres, telomerase and the T-cell costimulatory receptor, CD28, in modulating the process of CD8 T-cell replicative senescence and the impact of this process on aging and HIV disease.


Human Immunodeficiency Virus Human Immunodeficiency Virus Type Telomere Length Replicative Senescence Human Immunodeficiency Virus Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Ruscetti FW, Morgan DA, Gallo RC. Functional and morphologic characterization of human T-cells continuously grown in vitro. Journal of Immunology 1977; 119:131–8.Google Scholar
  2. 2.
    Paul WE, Sredni B, Schwartz RH. Long-term growth and cloning of nontransformed lymphocytes. Nature 1981; 294:697–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Perillo NL, Walford RL, Newman MA et al. Human T-lymphocytes possess a limited in vitro life span. Experimental Gerontology 1989; 24:177–87.PubMedCrossRefGoogle Scholar
  4. 4.
    Chiu CP, Harley CB. Replicative senescence and cell immortality: the role of telomeres and telomerase. Proceedings Of The Society For Experimental Biology And Medicine. Society For Experimental Biology And Medicine 1977; 214:99–106.Google Scholar
  5. 5.
    Adibzadeh M, Pohla H, Rehbein A et al. Long-term culture of monoclonal human T-lymphocytes: models for immunosenescence? Mechanisms of Ageing and Development 1995; 83:171–83.PubMedCrossRefGoogle Scholar
  6. 6.
    Grubeck-Loebenstein B, Lechner H, Trieb K. Long-term in vitro growth of human T-cell clones: can postmitotic’ senescent’ cell populations be defined? International Archives Of Allergy And Immunology 1994; 104:232–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Spaulding C, Guo W, Effros RB. Resistance to apoptosis in human CD8+ T-cells that reach replicative senescence after multiple rounds of antigen-specific proliferation. Experimental Gerontology 1999; 34:633–44.PubMedCrossRefGoogle Scholar
  8. 8.
    Bryant JE, Hutchings KG, Moyzis RK et al. Measurement of telomeric DNA content in human tissues. Biotechniques 1997; 23:476–8, 480, 482, passim.PubMedGoogle Scholar
  9. 9.
    Effros RB, Boucher N, Porter V et al. Decline in CD28+ T-cells in centenarians and in long-term T-cell cultures: A possible cause for both in vivo and in vitro immunosenescence. Experimental Gerontology 1994; 29:601–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Effros RB, Pawelec G. Replicative senescence of T-cells: does the Hayflick Limit lead to immune exhaustion? Immunology Today 1997; 18:450–4.PubMedCrossRefGoogle Scholar
  11. 11.
    Perillo NL, Naeim F, Walford RL et al. The in vitro senescence of human T-lymphocytes: Failure to divide is not associated with a loss of cytolytic activity or memory T-cell phenotype. Mechanisms of Ageing and Development 1993; 67:173–85.PubMedCrossRefGoogle Scholar
  12. 12.
    Posnett DN, Sinha R, Kabak S et al. Clonal populations of T-cells in normal elderly humans: the T-cell equivalent to “benign monoclonal gammapathy”. Journal of Experimental Medicine 1994; 179:609–18.PubMedCrossRefGoogle Scholar
  13. 13.
    Thoman ML, Weigle WO. The cellular and subcellular bases of immunosenescence. Advances In Immunology 1989; 46:221–61.PubMedCrossRefGoogle Scholar
  14. 14.
    Murasko DM, Weiner P, Kaye D. Decline in mitogen induced proliferation of lymphocytes with increasing age. Clincal and Experimental Immunology 1987; 70:440–8.Google Scholar
  15. 15.
    Grossmann A, Ledbetter JA, Rabinovitch PS. Reduced proliferation in T-lymphocytes in aged humans is predominantly in the CD8+ subset and is unrelated to defects in transmembrane signaling which are predominantly in the CD4+ subnet. Experimental Cell Research 1989; 180:367–82.PubMedCrossRefGoogle Scholar
  16. 16.
    Franceschi C, Bonafe M, Valensin S. Human immunosenescence: the prevailing of innate immunity, the failing of clonotypic immunity and the filling of immunological space. Vaccine 2000; 18:1717–20.PubMedCrossRefGoogle Scholar
  17. 17.
    Goronzy JJ, Fulbright JW, Crowson CS et al. Value of immunological markers in predicting responsiveness to influenza vaccination in elderly individuals. Journal Of Virology 2001; 75:12182–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Saurwein-Teissl M, Lung TL, Marx F et al. 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. Journal Of Immunology 2002; 168:5893–9.Google Scholar
  19. 19.
    Looney RJ, Falsey A, Campbell D et al. Role of Cytomegalovirus in the T-cell Changes Seen in Elderly Individuals. Clinical Immunology 1999; 90:213–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Suciu-Foca N, Manavalan JS, Scotto L et al. Molecular characterization of allospecific T suppressor and tolerogenic dendritic cells: review. International Immunopharmacology 2005; 5:7–11.PubMedCrossRefGoogle Scholar
  21. 21.
    Rocha B, Dautigny N, Pereira P. Peripheral T-lymphocytes: expansion potential and homeostatic regulation of pool sizes and CD4/CD8 ratios in vivo. European Journal of Immunology 1989; 19:905–11.PubMedCrossRefGoogle Scholar
  22. 22.
    Freitas AA, Agenes F, Coutinho GC. Cellular competition modulates survival and selection of CD8+ T-cells. European Journal of Immunology 1996; 26:2640–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Monteiro J, Batliwalla F, Ostrer H et al. Shortened telomeres in clonally expanded CD28-CD8+ T-cells imply a replicative history that is distinct from their CD28+CD8+ counterparts. Journal Of Immunology 1996; 156:3587–90.Google Scholar
  24. 24.
    Effros RB, Allsopp R, Chiu CP et al. Shortened telomeres in the expanded CD28-CD8+ cell subset in HIV disease implicate replicative senescence in HIV pathogenesis. AIDS 1996; 10:F17–F22.PubMedCrossRefGoogle Scholar
  25. 25.
    Blackburn EH. Structure and function of telomeres. Nature 1991; 350:569–73.PubMedCrossRefGoogle Scholar
  26. 26.
    Allsopp RC. Models of initiation of replicative senescence by loss of telomeric DNA. Experimental Gerontology 1996; 31:235–43.PubMedCrossRefGoogle Scholar
  27. 27.
    Lundblad V, Szostak JW. A mutant with a defect in telomere elongation leads to senescence in yeast. Cell 1989; 57:633–43.PubMedCrossRefGoogle Scholar
  28. 28.
    Allsopp RC, Vaziri H, Patterson C et al. Telomere length predicts replicative capacity of human fibroblasts. Proceedings of the National Academy of Sciences 1992; 89:10114–8.CrossRefGoogle Scholar
  29. 29.
    Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature 1990; 345:458–60.PubMedCrossRefGoogle Scholar
  30. 30.
    Olovnikov AM. [Principle of marginotomy in template synthesis of polynucleotides]. Dokl Akad Nauk SSSR 1971; 201:1496–9.PubMedGoogle Scholar
  31. 31.
    Watson JD. Origin of concatemeric T7 DNA. National New Biology 1972; 239:197–201.CrossRefGoogle Scholar
  32. 32.
    Bodnar AG, Ouellette M, Frolkis M et al. Extension of life-span by introduction of telomerase into normal human cells. Science 1998; 279:349–52.PubMedCrossRefGoogle Scholar
  33. 33.
    Vaziri H, Benchimol S. Reconstitution of telomerase activity in normal human cells leads to elongation of telomeres and extended replicative life span. Current Biology 1998; 8:279–82.PubMedCrossRefGoogle Scholar
  34. 34.
    Dagarag M, Evazyan T, Rao N et al. Genetic manipulation of telomerase in HIV-specific CD8+ T-cells: enhanced antiviral functions accompany the increased proliferative potential and telomere length stabilization. Journal of Immunology 2004; 173:6303–11.Google Scholar
  35. 35.
    Pawelec G, Wagner W, Adibzadeh M et al. T-cell immunosenescence in vitro and in vivo. Experimental Gerontology 1999; 34:419–29.PubMedCrossRefGoogle Scholar
  36. 36.
    Erickson S, Sangfelt O, Heyman M et al. Involvement of the Ink4 proteins p16 and p15 in T-lymphocyte senescence. Oncogene 1998; 17:595–602.PubMedCrossRefGoogle Scholar
  37. 37.
    Vaziri H, Schachter F, Uchida I et al. Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes. American Journal Of Human Genetics 1993; 52:661–7.PubMedGoogle Scholar
  38. 38.
    Weng NP, Levine BL, June CH et al. Human naive and memory T-lymphocytes differ in telomeric length and replicative potential. Proceedings Of The National Academy Of Sciences 1995; 92:11091–4.CrossRefGoogle Scholar
  39. 39.
    Son NH, Murray S, Yanovski J et al. Lineage-specific telomere shortening and unaltered capacity for telomerase expression in human T and B-lymphocytes with age. Journal Of Immunology 2000; 165:1191–6.Google Scholar
  40. 40.
    Campisi J. Cellular senescence as a tumor-suppressor mechanism. Trends in Cell Biology 2001; 11: S27–S31.PubMedGoogle Scholar
  41. 41.
    Boucher N, Dufeu-Duchesne T, Vicaut E et al. CD28 Expression in T-cell Aging and Human Longevity. Experimental Gerontology 1998; 33:267–82.PubMedCrossRefGoogle Scholar
  42. 42.
    Cawthon RM, Smith KR, O’Brien E et al. Association between telomere length in blood and mortality in people aged 60 years or older. Lancet 2003; 361:393–5.PubMedCrossRefGoogle Scholar
  43. 43.
    Plunkett FJ, Soares MV, Annels N et al. The flow cytometric analysis of telomere length in antigen-specific CD8+ T-cells during acute Epstein-Barr virus infection. Blood 2001; 97:700–7.PubMedCrossRefGoogle Scholar
  44. 44.
    Rangan SR, Armatis P. Enhanced frequency of spontaneous B cell lines from Epstein-Barr virus (EBV) seropositive donors 80 years and older. Experimental Gerontology 1991; 26:541–7.PubMedCrossRefGoogle Scholar
  45. 45.
    Valenzuela HF, Effros RB. Divergent telomerase and CD28 expression patterns in human CD4 and CD8 T-cells following repeated encounters with the same antigenic stimulus. Clinical Immunology 2002; 105:117–25.PubMedCrossRefGoogle Scholar
  46. 46.
    Jenkins MK, Taylor PS, Norton SD et al. CD28 delivers a costimulatory signal involved in antigen-specific IL-2 production by human T-cells. Journal Of Immunology 1991; 147:2461–6.Google Scholar
  47. 47.
    Sozou PD, Kirkwood TBL. A Stochastic Model of Cell Replicative Senescence Based on Telomere Shortening, Oxidative Stress and Somatic Mutations in Nuclear and Mitochondrial DNA. Journal of Theoretical Biology 2001; 213:573–86.PubMedCrossRefGoogle Scholar
  48. 48.
    Shimizu Y, van Seventer GA, Ennis E et al. Crosslinking of the T-cell-specific accessory molecules CD7 and CD28 modulates T-cell adhesion. Journal of Experimental Medicine 1992; 175:577–82.PubMedCrossRefGoogle Scholar
  49. 49.
    Frauwirth KA, Riley JL, Harris MH et al. The CD28 signaling pathway regulates glucose metabolism. Immunity. 2002; 16:769–77.PubMedCrossRefGoogle Scholar
  50. 50.
    Verweij CL, Geerts M, Aarden LA. Activation of interleukin-2 gene transcription via the T-cell surface molecule CD28 is mediated through an NF-kB-like response element. The Journal Of Biological Chemistry 1991; 266:14179–82.PubMedGoogle Scholar
  51. 51.
    Vallejo AN, Brandes JC, Weyand CM et al. Modulation of CD28 expression: distinct regulatory pathways during activation and replicative senescence. Journal Of Immunology 1999; 162:6572–9.Google Scholar
  52. 52.
    June CH, Bluestone JA, Nadler LM, Thompson CB. The B7 and CD28 receptor families. Immunology Today 1994; 15:321–31.PubMedCrossRefGoogle Scholar
  53. 53.
    Azuma M, Cayabyab M, Phillips JH et al. Requirements for CD28-dependent T-cell-mediated cytotoxicity. Journal Of Immunology 1993; 150:2091–101.Google Scholar
  54. 54.
    Tan P, Anasetti C, Hansen JA et al. Induction of alloantigen-specific hyporesponsiveness in human T-lymphocytes by blocking interaction of CD28 with its natural ligand B7/BB1. The Journal Of Experimental Medicine 1993; 177:165–73.PubMedCrossRefGoogle Scholar
  55. 55.
    Azuma M, Phillips JH, Lanier LL. CD28-T-lymphocytes. Antigenic and functional properties. Journal Of Immunology 1993; 150:1147–59.Google Scholar
  56. 56.
    Effros RB. Replicative senescence in the immune system: impact of the Hayflick limit on T-cell function in the elderly. American Journal of Human Genetics 1998; 62:1003–7.PubMedCrossRefGoogle Scholar
  57. 57.
    Posnett DN, Edinger JW, Manavalan JS et al. Differentiation of human CD8 T-cells: implications for in vivo persistence of CD8+ CD28-cytotoxic effector clones. International Immunology 1999; 11:229–41.PubMedCrossRefGoogle Scholar
  58. 58.
    Pawelec G, Akbar A, Caruso C et al. Is immunosenescence infectious? Trends in Immunology 2004; 25:406–10.PubMedCrossRefGoogle Scholar
  59. 59.
    Schwab R, Szabo P, Manavalan JS et al. Expanded CD4+ and CD8+ T-cell clones in elderly humans. Journal of Immunology 1997; 158:4493–9.Google Scholar
  60. 60.
    Chan SR, Blackburn EH. Telomeres and telomerase. Philosophical Transactions of the Royal London Society B: Biological Sciences 2004; 359:109–21.CrossRefGoogle Scholar
  61. 61.
    Blackburn EH. Telomerases. Annual Review of Biochemistry 1992; 61:113–29.PubMedCrossRefGoogle Scholar
  62. 62.
    Greider CW. Telomeres, telomerase and senescence. Bioessays 1990; 12:363–9.PubMedCrossRefGoogle Scholar
  63. 63.
    Yang J, Chang E, Cherry AM et al. Human endothelial cell life extension by telomerase expression. The Journal Of Biological Chemistry 1999; 274:26141–8.PubMedCrossRefGoogle Scholar
  64. 64.
    Luiten RM, Pene J, Yssel H et al. Ectopic hTERT expression extends the life span of human CD4+ helper and regulatory T-cell clones and confers resistance to oxidative stress-induced apoptosis. Blood 2003; 101:4512–9.PubMedCrossRefGoogle Scholar
  65. 65.
    Counter CM, Avilion AA, LeFeuvre CE et al. Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. The EMBO Journal 1992; 11:1921–9.PubMedGoogle Scholar
  66. 66.
    Kim NW, Piatyszek MA, Prowse KR et al. Specific association of human telomerase activity with immortal cells and cancer. Science 1994; 266:2011–5.PubMedCrossRefGoogle Scholar
  67. 67.
    Igarashi H, Sakaguchi N. Telomerase Activity Is Induced by the Stimulation to Antigen Receptor in Human Peripheral Lymphocytes. Biochemical and Biophysical Research Communications 1996; 219:649–55.PubMedCrossRefGoogle Scholar
  68. 68.
    Broccoli D, Young JW, de Lange T. Telomerase activity in normal and malignant hematopoietic cells. Proceedings Of The National Academy Of Sciences 1995; 92:9082–6.CrossRefGoogle Scholar
  69. 69.
    Weng NP, Levine BL, June CH et al. Regulated expression of telomerase activity in human T-lymphocyte development and activation. Journal of Experimental Medicine 1996; 183:2471–9.PubMedCrossRefGoogle Scholar
  70. 70.
    Hiyama K, Hirai Y, Kyoizumi S et al. Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. Journal of Immunology 1995; 155:3711–5.Google Scholar
  71. 71.
    Weng N, Levine BL, June CH et al. Regulation of telomerase RNA template expression in human T-lymphocyte development and activation. Journal Of Immunology 1997; 158:3215–20.Google Scholar
  72. 72.
    Maini MK, Soares MV, Zilch CF et al. Virus-induced CD8+ T-cell clonal expansion is associated with telomerase up-regulation and telomere length preservation: a mechanism for rescue from replicative senescence. Journal Of Immunology 1999; 162:4521–6.Google Scholar
  73. 73.
    Roth A, Yssel H, Pene J et al. Telomerase levels control the lifespan of human T-lymphocytes. Blood 2003; 102:849–57.PubMedCrossRefGoogle Scholar
  74. 74.
    Weng NP, Palmer LD, Levine BL et al. Tales of tails: regulation of telomere length and telomerase activity during lymphocyte development, differentiation, activation and aging. Immunology Review 1997; 160:43–54.CrossRefGoogle Scholar
  75. 75.
    Bodnar AG, Kim NW, Effros RB et al. Mechanism of telomerase induction during T-cell activation. Experimental Cell Research 1996; 228:58–64.PubMedCrossRefGoogle Scholar
  76. 76.
    Rufer N, Migliaccio M, Antonchuk J et al. Transfer of the human telomerase reverse transcriptase (TERT) gene into T-lymphocytes results in extension of replicative potential. Blood 2001; 98:597–603.PubMedCrossRefGoogle Scholar
  77. 77.
    Hooijberg E, Ruizendaal JJ, Snijders PJ et al. Immortalization of human CD8+ T-cell clones by ectopic expression of telomerase reverse transcriptase. Journal of Immunology 2000; 165:4239–45.Google Scholar
  78. 78.
    Dagarag M, Ng H, Lubong R et al. Differential impairment of lytic and cytokine functions in senescent human immunodeficiency virus type 1-specific cytotoxic T-lymphocytes. Journal of Virology 2003; 77:3077–83.PubMedCrossRefGoogle Scholar
  79. 79.
    Yang OO, Walker BD. CD8+ cells in human immunodeficiency virus type I pathogenesis: cytolytic and noncytolytic inhibition of viral replication. Advanced Immunology 1997; 66:273–311.CrossRefGoogle Scholar
  80. 80.
    Borrow P, Lewicki H, Hahn BH et al. Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection. Journal of Virology 1994; 68:6103–10.PubMedGoogle Scholar
  81. 81.
    Koup RA, Safrit JT, Cao Y et al. Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. Journal of Virology 1994; 68:4650–5.PubMedGoogle Scholar
  82. 82.
    Ogg GS, Jin X, Bonhoeffer S et al. Quantitation of HIV-1-specific cytotoxic T-lymphocytes and plasma load of viral RNA. Science 1998; 279:2103–6.PubMedCrossRefGoogle Scholar
  83. 83.
    Bailer RT, Holloway A, Sun J et al. IL-13 and IFN-gamma secretion by activated T-cells in HIV-1 infection associated with viral suppression and a lack of disease progression. Journal of Immunology 1999; 162:7534–42.Google Scholar
  84. 84.
    Garzino-Demo A, Moss RB, Margolick JB et al. Spontaneous and antigen-induced production of HIV-inhibitory beta-chemokines are associated with AIDS-free status. Proceedings Of The National Academy Of Sciences 1999; 96:11986–91.CrossRefGoogle Scholar
  85. 85.
    Buseyne F, Fevrier M, Garcia S et al. Dual function of a human immunodeficiency virus (HIV)-specific cytotoxic T-lymphocyte clone: inhibition of HIV replication by noncytolytic mechanisms and lysis of HIV-infected CD4+ cells. Virology 1996; 225:248–53.PubMedCrossRefGoogle Scholar
  86. 86.
    Daar ES, Moudgil T, Meyer RD et al. Transient high levels of viremia in patients with primary human immunodeficiency virus type 1 infection. The New England Journal of Medicine 1991; 324:961–4.PubMedCrossRefGoogle Scholar
  87. 87.
    Clark SJ, Saag MS, Decker WD et al. High titers of cytopathic virus in plasma of patients with symptomatic primary HIV-1 infection. The New England Journal of Medicine 1991; 324:954–60.PubMedGoogle Scholar
  88. 88.
    Lieberman J, Shankar P, Manjunath N et al. Dressed to kill? A review of why antiviral CD8 T-lymphocytes fail to prevent progressive immunodeficiency in HIV-1 infection. Blood 2001; 98:1667–77.PubMedCrossRefGoogle Scholar
  89. 89.
    Cao Y, Qin L, Zhang L et al. Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection. The New England Journal Of Medicine 1995; 332:201–8.PubMedCrossRefGoogle Scholar
  90. 90.
    Harrer T, Harrer E, Kalams SA et al. Cytotoxic T-lymphocytes in asymptomatic long-term nonprogressing HIV-1 infection. Breadth and specificity of the response and relation to in vivo viral quasispecies in a person with prolonged infection and low viral load. Journal Of Immunology 1996; 156:2616–23.Google Scholar
  91. 91.
    Shankar P, Russo M, Harnisch B et al. Impaired function of circulating HIV-specific CD8(+) T-cells in chronic human immunodeficiency virus infection. Blood 2000; 96:3094–101.PubMedGoogle Scholar
  92. 92.
    Borthwick NJ, Bofill M, Gombert WM et al. Lymphocyte activation in HIV-1 infection. II. Functional defects of CD28-T-cells. AIDS 1994; 8:431–41.PubMedCrossRefGoogle Scholar
  93. 93.
    Lewis DE, Tang DS, Adu-Oppong A et al. Anergy and apoptosis in CD8+ T-cells from HIV-infected persons. Journal Of Immunology 1994; 153:412–20.Google Scholar
  94. 94.
    Brinchmann JE, Dobloug JH, Heger BH et al. Expression of costimulatory molecule CD28 on T-cells in human immunodeficiency virus type 1 infection: functional and clinical correlations. The Journal Of Infectious Diseases 1994; 169:730–8.PubMedGoogle Scholar
  95. 95.
    Khan N, Shariff N, Cobbold M et al. Cytomegalovirus seropositivity drives the CD8 T-cell repertoire toward greater clonality in healthy elderly individuals. Journal Of Immunology 2002; 169:1984–92.Google Scholar
  96. 96.
    van Baarle D, Tsegaye A, Miedema F et al. Significance of senescence for virus-specific memory T-cell responses: rapid ageing during chronic stimulation of the immune system. Immunology Letters 2005; 97:19–29.PubMedCrossRefGoogle Scholar
  97. 97.
    Tripp RA, Hou S, McMickle A et al. Recruitment and proliferation of CD8+ T-cells in respiratory virus infections. Journal of Immunology 1995; 154:6013–21.Google Scholar
  98. 98.
    Appay V, Rowland-Jones SL. Premature ageing of the immune system: the cause of AIDS? Trends in Immunology 2002; 23:580–5.PubMedCrossRefGoogle Scholar
  99. 99.
    Palmer LD, Weng N, Levine BL et al. Telomere length, telomerase activity and replicative potential in HIV infection: analysis of CD4+ and CD8+ T-cells from HIV-discordant monozygotic twins. Journal of Experimental Medicine 1997; 185:1381–6.PubMedCrossRefGoogle Scholar
  100. 100.
    Wolthers KC, Miedema F. Telomeres and HIV-1 infection: in search of exhaustion. Trends in Microbiology 1998; 6:144–7.PubMedCrossRefGoogle Scholar
  101. 101.
    Bestilny LJ, Gill MJ, Mody CH et al. Accelerated replicative senescence of the peripheral immune system induced by HIV infection. AIDS 2000; 14:771–80.PubMedCrossRefGoogle Scholar
  102. 102.
    Lane HC, Laughon BE, Falloon J et al. NIH conference. Recent advances in the management of AIDS-related opportunistic infections. Annals of Internal Medicine 1994; 120:945–55.PubMedGoogle Scholar
  103. 103.
    Kalayjian RC, Cohen ML, Bonomo RA et al. Cytomegalovirus ventriculoencephalitis in AIDS. A syndrome with distinct clinical and pathologic features. Medicine 1993; 72:67–77.PubMedCrossRefGoogle Scholar
  104. 104.
    Chitale AR. Cancer and AIDS. Indian Journal of Pathology and Microbiology 2005; 48:151–60.Google Scholar
  105. 105.
    Tucker V, Jenkins J, Gilmour J et al. T-cell telomere length maintained in HIV-infected long-term survivors. HIV Medicine 2000; 1:116–22.PubMedCrossRefGoogle Scholar
  106. 106.
    Wolthers KC, Bea G, Wisman A et al. T-cell telomere length in HIV-1 infection: no evidence for increased CD4+ T-cell turnover. Science 1996; 274:1543–7.PubMedCrossRefGoogle Scholar
  107. 107.
    Pommier JP, Gauthier L, Livartowski J et al. Immunosenescence in HIV Pathogenesis. Virology 1997; 231:148–54.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2007

Authors and Affiliations

  • Steven R. Fauce
    • 1
  • Rita B. Effros
    • 1
  1. 1.Department of Pathology and Laboratory MedicineDavid Geffen School of Medicine at UCLALos AngelesUSA

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