Impaired apoptosis and immune senescence - Cause or effect?

Immunological Reviews

Volumn 205, Issue , 2005, Pages 130-146

  Hsu, Hui Chen ^a   Scott, Donald K ^b   Mountz, John D ^a,c,d  

^a The University of Alabama at Birmingham   (United States)

^b LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER   (United States)

^c BIRMINGHAM VA MEDICAL CENTER   (United States)

^d UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AUTOANTIBODY; AUTOANTIGEN; B7 ANTIGEN; CD28 ANTIGEN; CD3 ANTIGEN; FAS ANTIGEN; FAS LIGAND; T LYMPHOCYTE RECEPTOR;

AGING; ANTIBODY PRODUCTION; APOPTOSIS; AUTOIMMUNITY; CELLULAR IMMUNODEFICIENCY; CYTOTOXIC T LYMPHOCYTE; HUMAN; IMMUNOLOGICAL TOLERANCE; IMMUNOREACTIVITY; IMMUNOREGULATION; LYMPHOCYTOPOIESIS; NONHUMAN; POLYCLONAL ACTIVATION; PRIORITY JOURNAL; REVIEW; T LYMPHOCYTE ACTIVATION; T LYMPHOCYTE SUBPOPULATION; TH1 CELL; TH2 CELL;

AGING; ANIMALS; ANTIGENS, CD; APOPTOSIS; FAS LIGAND PROTEIN; HUMANS; MEMBRANE GLYCOPROTEINS; SIGNAL TRANSDUCTION; T-LYMPHOCYTES;

EID: 20344399856     PISSN: 01052896     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.0105-2896.2005.00270.x     Document Type: Review

References (125)

1. Rea IM, McNerlan SE, Alexander HD. CD69, CD25, and HLA-DR activation antigen expression on CD3+ lymphocytes and relationship to serum TNF-alpha, IFN-gamma, and sIL-2R levels in aging. Exp Gerontol 1999;34:79-93.
2. Bryl E, Vallejo AN, Weyand CM, Goronzy JJ. Down-regulation of CD28 expression by TNF-alpha. J Immunol 2001;167:3231-3238.
3. 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. Exp Gerontol 1999;34:633-644.
4. Hsu HC, et al. Activated CD8 (+) T cells from aged mice exhibit decreased activation-induced cell death. Mech Ageing Dev 2001;122:1663-1684.
5. Vallejo AN, Brandes JC, Weyand CM, Goronzy JJ. Modulation of CD28 expression: distinct regulatory pathways during activation and replicative senescence. J Immunol 1999;162:6572-6579.
6. Vallejo AN, Nestel AR, Schirmer M, Weyand CM, Goronzy JJ. Aging-related deficiency of CD28 expression in CD4+ T cells is associated with the loss of gene-specific nuclear factor binding activity. J Biol Chem 1998;273:8119-8129.
7. Warrington KJ, Vallejo AN, Weyand CM, Goronzy JJ. CD28 loss in senescent CD4+ T cells: reversal by interleukin-12 stimulation. Blood 2003;101:3543-3549.
8. Zhang Y, Wang Y, Gilmore X, Xu K, Mbawuike IN. Independent and synergistic effects of interleukin-18 and interleukin-12 in augmenting cytotoxic T lymphocyte responses and IFN-gamma production in aging. J Interferon Cytokine Res 2001;21:843-850.
9. Hsu HC, et al. Aged mice exhibit in vivo defective peripheral clonal deletion of D(b)/ H-Y reactive CD8 (+) T cells. Mech Ageing Dev 2001;122:305-326.
10. Zhou T, Edwards CK III, Mountz JD. Prevention of age-related T cell apoptosis defect in CD2-fas-transgenic mice. J Exp Med 1995;182:129-137.
11. Jiang J, Anaraki F, Blank KJ, Murasko DM. Cuttine edge: T cells from aged mice are resistant to depletion early during virus infection. J Immunol 2003;171:3353-3357.
12. Hsu HC, Zhou T, Yang PA, Herrera GA, Mountz JD. Increased acute-phase response and renal amyloidosis in aged CD2-fas-transgenic mice. J Immunol 1997;158:5988-5996.
13. Hajra KM, Liu JR. Apoptosome dysfunction in human cancer. Apoptosis 2004;9:691-704.
14. Zhou T, Mountz JD, Kimberly RP. Immunobiology of tumor necrosis factor receptor superfamily. Immunol Res 2002;26:323-336.
15. Effros RB. Long-term immunological memory against viruses. Mech Ageing Dev 2000;121:161-171.
16. Ku CC, Kappler J, Marrack P. The growth of the very large CD8+ T cell clones in older mice is controlled by cytokines. J Immunol 2001;166:2186-2193.
17. Effros RB. Costimulatory mechanisms in the elderly. Vaccine 2000;18:1661-1665.
18. Maini MK, Scares MV, Zilch CF, Akbar AN, Beverley PC. Virus-induced CD8+ T cell clonal expansion is associated with telomerase up-regulation and telomere length preservation: a mechanism for rescue from replicative senescence. J Immunol 1999;162:4521-4526.
19. Wack A, et al. Age-related modifications of the human alphabeta T cell repertoire due to different clonal expansions in the CD4+ and CD8+ subsets. Int Immunol 1998;10:1281-1288.
20. Li F, et al. Tumor antigen drives a persistent oligoclonal expansion of CD8+ T cells in aged mice. Eur J Immunol 2002;32:1650-1658.
21. Schwab R, et al. Expanded CD4+ and CD8+ T cell clones in elderly humans. J Immunol 1997;158:4493-4499.
22. Callahan JE, Kappler JW, Marrack P. Unexpected expansions of CD8-bearing cells in old mice. J Immunol 1993;151:6657-6669.
23. Ku CC, Kotzin B, Kappler J, Marrack P. CD8+ T-cell clones in old mice. Immunol Rev 1997;160:139-144.
24. Posnett DN, Sinha R, Kabak S, Russo C. Clonal populations of T cells in normal elderly humans: the T cell equivalent to 'benign monoclonal gammapathy'. J Exp Med 1994;179:609-618.
25. Posnett DN, Edinger JW, Manavalan JS, Irwin C, Marodon G. Differentiation of human CDS T cells, implications for in vivo persistence of CD8+ CD28-cytotoxic effector clones. Int Immunol 1999;11:229-241.
26. McCarron M, Osborne Y, Story CJ, Dempsey JL, Turner DR, Morley AA. Effect of age on lymphocyte proliferation. Mech Ageing Dev 1987;41:211-218.
27. Adibzadeh M, Pohla H, Rehbein A, Pawelec G. Long-term culture of monoclonal human T lymphocytes: models for immunosenescence? Mech Ageing Dev 1995;83:171-183.
28. Adibzadeh M, et al. Lifespans of T lymphocytes. Mech Ageing Dev 1996;91:145-154.
29. McLean AR, Michie CA. In vivo estimates of division and death rates of human T lymphocytes. Proc Natl Acad Sci USA 1995;92:3707-3711.
30. Plunkett FJ, Soares MV, Salmon M, Akbar AN. Regulation of apoptosis and replicative senescence in CD8+ T cell following acute viral infection. Apoptosis 2000;5:431-434.
31. Akbar AN, Soares MV, Plunkett FJ, Salmon M. Differential regulation of CD8+ T cell senescence in mice and men. Mech Ageing Dev 2000;121:69-76.
32. Van Parijs L, Ibraghimov A, Abbas AK. The roles of costimulation and Fas in T cell apoptosis and peripheral tolerance. Immunity 1996;4:321-328.
33. Kabelitz D, Janssen O. Antigen-induced death of T-Lymphocytes. Front Biosci 1997;2:d61-d77.
34. Zhang J, et al. Regulation of fas ligand expression during activation-induced cell death in T cells by p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase. J Exp Med 2000;191:1017-1030.
35. Zhang J, Bardos T, Mikecz K, Finnegan A, Glant TT. Impaired Fas signaling pathway is involved in defective T cell apoptosis in autoimmune murine arthritis. J Immunol 2001;166:4981-4986.
36. van Parijs L, Perez VL, Abbas AK. Mechanisms of peripheral T cell tolerance. Novartis Found Symp 1998;215:5-14; discussion 14-20, 33-40.
37. Quadri RA, Piastre O, Phelouzat MA, Arbogast A, Proust JJ. Age-related tyrosine-specific protein phosphorylation defect in human T lymphocytes activated through CD3, CD4, CD8 or the IL-2 receptor. Mech Ageing Dev 1996;88:125-138.
38. Phelouzat MA, Arbogast A, Laforge T, Quadri RA, Proust JJ. Excessive apoptosis of mature T lymphocytes is a characteristic feature of human immune senescence. Mech Ageing Dev 1996;88:25-38.
39. Miller RA, Garcia G, Kirk CJ, Witkowski JM. Early activation defects in T lymphocytes from aged mice. Immunol Rev 1997;160:79-90.
40. Lyons AB, Parish CR. Determination of lymphocyte division by flow cytometry. J Immunol Meth 1994;171:131-137.
41. Fagnoni FF, et al. Shortage of circulating naive CD8 (+) T cells provides new insights on immunodeficiency in aging. Blood 2000;95:2860-2868.
42. Spaulding C, Walford RL, Effros RB. The accumulation of nonreplicative, nonfunctional, senescent T cells with age is avoided in calorially restricted mice by an enhancement of Tcell apoptosis. Mech Ageing Dev 1997;93:25-23.
43. Aggarwal S, Gollapudi S, Gupca S. Increased TNF-alpha-induced apoptosis in lymphocytes from aged humans: changes in TNF-alpha receptor expression and activation of caspases. J Immunol 1999;162:2154-2161.
44. Gupta S. Tumor necrosis factor-alpha-induced apoptosis in T cells from aged humans: a role of TNFR-I and downstream signaling molecules. Exp Gerontol 2000;37:293-299.
45. Dennett NS, Barcia RN, McLeod JD. Age associated decline in CD25 and CD28 expression correlate with an increased susceptibility to CD95 mediated apoptosis in T cells. Exp Gerontol 2002;37:271-283.
46. Phelouzat MA, Laforge T, Arbogast A, Quadri RA, Boutet S, Proust JJ. Susceptibility to apoptosis of T lymphocytes from elderly humans is associated with increased in vivo expression of functional Fas receptors. Mech Ageing Dev 1997;96:35-46.
47. Bryl E, Gazda M, Foerster J, Witkowski JM. Age-related increase of frequency of a new, phenotypically distinct subpopulation of human peripheral blood T cells expressing lowered levels of CD4. Blood 2001;98:1100-1107.
48. Spaulding CC, Walford RL, Effros RB. The accumulation of non-replicative, non-functional, senescent T cells with age is avoided in calorically restricted mice by an enhancement of T cell apoptosis. Mech Ageing Dev 1997;93:25-33.
49. Herndon FJ, Hsu HC, Mountz JD. Increased apoptosis of CD45RO- T cells with aging. Mech Ageing Dev 1997;94:123-134.
50. Pinti M, et al. Balanced regulation of mRNA production for Fas and Fas ligand in lymphocytes from centenarians: how the immune system starts its second century. Circulation 2004;110:3108-3114.
51. Brunner T, Wasem C, Torgler R, Cima I, Jakob S, Corazza N. Fas (CD95/Apo-1) ligand regulation in T cell homeostasis, cell-mediated cytotoxicity and immune pathology. Semin Immunol 2003;15:167-176.
52. Griffiths GM. Protein sorting and secretion during CTL killing. Semin Immunol 1997;9:109-115.
53. Pham CT, Ley TJ. The role of granzyme B cluster proteases in cell-mediated cytotoxicity. Semin Immunol 1997;9:127-133.
54. Raja SM, Metkar SS, Froelich CJ. Cytotoxic granule-mediated apoptosis: unraveling the complex mechanism. Curr Opin Immunol 2003;15:528-532.
55. Pardo J, et al. Apoptotic pathways are selectively activated by granzyme A and/or granzyme B in CTL-mediated target cell lysis. J Cell Biol 2004;167:457-468.
56. Barry M, et al. Granzyme B short-circuits the need for caspase 8 activity during granule-mediated cytotoxic T-lymphocyte killing by directly cleaving Bid. Mol Cell Biol 2000;20:3781-3794.
57. Heibein JA, et al. Granzyme B-mediated cytochrome c release is regulated by the Bcl-2 family members bid and Bax. J Exp Med 2000;192:1391-1402.
58. Hamann D, et al. Phenotypic and functional separation of memory and effector human CD8+ T cells. J Exp Med 1997;186:1407-1418.
59. Ramsdell F, Seaman MS, Miller RE, Picha KS, Kennedy MK, Lynch DH. Differential ability of Th1 and Th2 T cells to express Fas ligand and to undergo activation-induced cell death. Int Immunol 1994;6:1545-1553.
60. Yahata T, et al. The essential role of phorbol ester-sensitive protein kinase C isoforms in activation-induced cell death of Th1 cells. Eur J Immunol 1999;29:727-732.
61. Varadhachary AS, Perdow SN, Hu C, Ramanarayanan M, Salgame P. Differential ability of T cell subsets to undergo activation-induced cell death. Proc Natl Acad Sci USA 1997;94:5778-5783.
62. Mallone R, Nepom GT. MHC class II tetramers and the pursuit of antigen-specific T cells: define, deviate, delete. Clin Immunol 2004;110:232-242.
63. Li-Weber M, Krammer PH. Function and regulation of the CD95 (APO-1/Fas) ligand in the immune system. Semin Immunol 2003;15:145-157.
64. Villalba M, Kasibhatla S, Genestier L, Mahboubi A, Green DR, Altman A. Protein kinase C theta cooperates with calcineurin to induce Fas ligand expression during activation-induced T cell death. J Immunol 1999;163:5813-5819.
65. Villunger A, et al. Synergistic action of protein kinase C theta and calcineurin is sufficient for Fas ligand expression and induction of a crmA-sensitive apoptosis pathway in Jurkat T cells. Eur J Immunol 1999;29:3549-3561.
66. Li-Weber M, Laur O, Krammer PH. Novel Egr/NF-AT composite sites mediate activation of the CD95 (APO-1/Fas) ligand promoter in response to T cell stimulation. Eur J Immunol 1999;29:3017-3027.
67. Brunner T, et al. Expression of Fas ligand in activated T cells is regulated by c-Myc. J Biol Chem 2000;275:9767-9772.
68. Wiener Z, et al. Synergistic induction of the Fas (CD95) ligand promoter by Max and NFkappaB in human non-small lung cancer cells. Exp Cell Res 2004;299:227-235.
69. Latinis KM, Carr LL, Pecerson EJ, Norian LA, Eliason SL, Koretzky GA. Regulation of CD95 (Fas) ligand expression by TCR-mediated signaling events. J Immunol 1997;158:4602-4611.
70. Hsu SC, Gavrilin MA, Lee HH, Wu CC, Han SH, Lai MZ. NF-kappa B-dependent Fas ligand expression. Eur J Immunol 1999;29:2948-2956.
71. Arendt CW, Albrecht B, Soos TJ, Littman DR. Protein kinase C-theta: signaling from the center of the T-cell synapse. Curr Opin Immunol 2002;14:323-330.
72. Eichhorst ST, Muller M, Li-Weber M, Schulze-Bergkamen H, Angel P, Krammer PH. A novel AP-1 elemenc in the CD95 ligand promoter is required for induction of apoptosis in hepatocellular carcinoma cells upon treatment with anticancer drugs. Mol Cell Biol 2000;20:7826-7837.
73. Faris M, Latinis KM, Kempiak SJ, Koretzky GA, Nel A. Stress-induced Fas ligand expression in T cells is mediated through a MEK kinase 1-regulated response element in the Fas ligand promoter. Mol Cell Biol 1998;18:5414-5424.
74. Kasibhatla S, Brunner T, Genestier L, Echeverri F, Mahboubi A, Green DR. DNA damaging agents induce expression of Fas ligand and subsequent apoptosis in T lymphocytes via the activation of NF-kappa B and AP-1. Mol Cell 1998;1:543-551.
75. Latinis KM, Norian LA, Eliason SL, Koretzky GA. Two NFAT transcription factor binding sites participate in the regulation of CD95 (Fas) ligand expression in activated human T cells. J Biol Chem 1997;272:31427-31434.
76. Holtz-Heppelmann CJ, Algeciras A, Badley AD, Paya CV. Transcriptional regulation of the human FasL promoter-enhancer region. J Biol Chem 1998;273:4416-4423.
77. Li-Weber M, Laur O, Hekele A, Coy J, Walczak H, Krammer PH. A regulatory element in the CD95 (APO-1/Fas) ligand promoter is essential for responsiveness to TCR-mediated activation. Eur J Immunol 1998;28:2373-2383.
78. Farina A, Faiola F, Martinez E. Reconstitution of an E box-binding Myc: Max complex with recombinant full-length proteins expressed in Escherichia coli. Protein Expr Purif 2004;34:215-222.
79. Hueber AO, Zornig M, Lyon D, Suda T, Nagata S, Evan GI. Requirement for the CD95 receptor-ligand pathway in c-Myc-induced apoptosis. Science 1997;278:1305-1309.
80. Wang R, Brunner T, Zhang L, Shi Y. Fungal metabolite FR901228 inhibits c-Myc and Fas ligand expression. Oncogene 1998;17:1503-1508.
81. Whisler RL, Beiqing L, Chen M. Age-related decreases in IL-2 production by human T cells are associated wich impaired activation of nuclear transcriptional factors AP-1 and NF-AT. Cell Immunol 1996;169:185-195.
82. Garcia GG, Miller RA. Single-cell analyses reveal two defects in peptide-specific activation of naive T cells from aged mice. J Immunol 2001;166:3151-3157.
83. Kirk CJ, Miller RA. Analysis of Raf-1 activation in response Co TCR activation and costimulation in murine T-lymphocytes: effect of age. Cell Immunol 1998;190:33-42.
84. Kirk CJ, Freilich AM, Miller RA. Age-related decline in activation of JNK by TCR- and CD28-mediated signals in murine T-lymphocytes. Cell Immunol 1999;197:75-82.
85. Frauwirth KA, et al. The CD28 signaling pathway regulates glucose metabolism. Immunity 2002;16:769-777.
86. Faris M, et al. The c-Jun N-terminal kinase cascade plays a role in stress-induced apoptosis in Jurkat cells by up-regulating Fas ligand expression. J Immunol 1998;160:134-144.
87. Lin X, O'Mahony A, Mu Y, Geleziunas R, Greene WC. Protein kinase C-theta participates in NF-kappaB activation induced by CD3-CD28 costimulation through selective activation of IkappaB kinase beta. Mol Cell Biol 2000;20:2933-2940.
88. Li-Weber M, Laur O, Dern K, Krammer PH. T cell activation-induced and HIV tat-enhanced CD95 (APO-1/Fas) ligand transcription involves NF-kappaB. Eur J Immunol 2000;30:661-670.
89. Spencer NF, Poynter ME, Im SY, Daynes RA. Constitutive activation of NF-kappa B in an animal model of aging. Int Immunol 1997;9:1581-1588.
90. Pawelec G, Hirokawa K, Fulop T. Altered T cell signalling in ageing. Mech Ageing Dev 2001;122:1613-1637.
91. Acuto O, Michel F. CD28-mediated co-stimulation: a quantitative support for TCR signalling. Nat Rev Immunol 2003;3:939-951.
92. Zhang J, et al. Cutting edge: regulation of T cell activation threshold by CD28 costimulation through targeting Cbl-b for ubiquitination. J Immunol 2002;169:2236-2240.
93. Barthwal MK, et al. Negative regulation of mixed lineage kinase 3 by protein kinase B/ AKT leads to cell survival. J Biol Chem 2003;278:3897-3902.
94. Pugazhenthi S, et al. Akt/protein kinase B up-regulates Bcl-2 expression through cAMP-response element-binding protein. J Biol Chem 2000;275:10761-10766.
95. Leinninger GM, Backus C, Uhler MD, Lentz SI, Feldman EL. Phosphatidylinositol 3-kinase and Akt effectors mediate insulin-like growth factor-I neuroprotection in dorsal root ganglia neurons. FASEB J 2004;18:1544-1546.
96. Brunet A, et al. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 1999;96:857-868.
97. Stahl M, et al. The forkhead transcription factor FoxO regulates transcription of p27Kip1 and Bim in response to IL-2. J Immunol 2002;168:5024-5031.
98. Miyauchi H, Minamino T, Tateno K, Kunieda T, Toko H, Komuro I. Akt negatively regulates the in vitro lifespan of human endothelial cells via a p53/p21-dependent pathway. EMBO J 2004;23:212-220.
99. Pandiyan P, Gartner D, Soezeri O, Radbruch A, Schulze-Osthoff K, Brunner-Weinzierl MC. CD152 (CTLA-4) determines the unequal resistance of Th1 and Th2 cells against activation-induced cell death by a mechanism requiring PI3 kinase function. J Exp Med 2004;199:831-842.
100. Ahmed R, Gray D. Immunological memory and protective immunity: understanding their relation. Science 1996;272:54-60.
101. Murali-Krishna K, et al. Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection. Immunity 1998;8:177-187.
102. Lohman BL, Welsh RM. Apoptotic regulation of T cells and absence of immune deficiency in virus-infected gamma interferon receptor knockout mice. J Virol 1998;72:7815-7821.
103. Murali-Krishna K, Lau LL, Sambhara S, Lemonnier F, Altman J, Ahmed R. Persistence of memory CD8 T cells in MHC class I-deficient mice. Science 1999;286:1377-1381.
104. Soares MV, Maini MK, Beverley PC, Salmon M, Akbar AN. Regulation of apoptosis and replicative senescence in CD8+ T cells from patients with viral infections. Biochem Soc Trans 2000;28:255-258.
105. Kapasi ZF, Murali-Krishna K, McRae ML, Ahmed R. Defective generation but normal maintenance of memory T cells in old mice. Eur J Immunol 2002;32:1567-1573.
106. Kaech SM, Tan JT, Wherry EJ, Konieczny BT, Surh CD, Ahmed R. Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells. Nat Immunol 2003;4:1191-1198.
107. Crawley JB, Rawlinson L, Lali FV, Page TH, Saklatvala J, Foxwell BM. T cell proliferation in response to interleukins 2 and 7 requires p38MAP kinase activation. J Biol Chem 1997;272:15023-15027.
108. Kalayjian RC, et al. Age-related immune dysfunction in health and in human immunodeficiency virus (HIV) disease: association of age and HIV infection with naive CD8+ cell depletion, reduced expression of CD28 on CD8+ cells, and reduced thymic volumes. J Infect Dis 2003;187:1924-1933.
109. Okada H, et al. Extensive lymphopenia due to apoptosis of uninfected lymphocytes in acute measles patients. Arch Virol 2000;145:905-920.
110. Ouyang Q, et al. Large numbers of dysfunctional CD8+ T lymphocytes bearing receptors for a single dominant CMV epitope in the very old. J Clin Immunol 2003;23:247-257.
111. Ouyang Q, Wagner WM, Zheng W, Wikby A, Remarque EJ, Pawelec G. Dysfunctional CMV-specific CD8 (+) T cells accumulate in the elderly. Exp Gerontol 2004;39:607-613.
112. Po JL, Gardner EM, Anaraki F, Katsikis PD, Murasko DM. Age-associated decrease in virus-specific CD8+ T lymphocytes during primary influenza infection. Mech Ageing Dev 2002;123:1167-1181.
113. Meyer KC. The role of immunity in susceptibility to respiratory infection in the aging lung. Respir Physiol 2001;128:23-31.
114. Radvanyi LG, Raju K, Spaner D, Mills GB, Miller RG. Interleukin-2 reverses the defect in activation-induced apoptosis in T cells from autoimmune lpr mice. Cell Immunol 1998;183:1-12.
115. Roths JB, Murphy ED, Eicher EM. A new mutation, gld, that produces lymphoproliferation and autoimmunity in C3H/HeJ mice. J Exp Med 1984;159:1-20.
116. Kobayashi M, Yasui N, Ishimaru N, Arakaki R, Hayashi Y. Development of autoimmune arthritis with aging via bystander T cell activation in the mouse model of Sjogren's syndrome. Arthritis Rheum 2004;50:3974-3984.
117. Koetz K, Bryl E, Spickschen K, O'Fallon WM, Goronzy JJ, Weyand CM. T cell homeostasis in patients with rheumatoid arthritis. Proc Natl Acad Sci USA 2000;97:9203-9208.
118. Santiago-Raber ML, et al. Role of cyclin kinase inhibitor p21 in systemic autoimmunity. J Immunol 2001;167:4067-4074.
119. Salvador JM, et al. Mice lacking the p53-effector gene Gadd45a develop a lupus-like syndrome. Immunity 2002;16:499-508.
120. Bird J, Ostler EL, Faragher RG. Can we say that senescent cells cause ageing? Exp Gerontol 2003;38:1319-1326.
121. Foreman KE, Tang J. Molecular mechanisms of replicative senescence in endothelial cells. Exp Gerontol 2003;38:1251-1257.
122. Han JH, et al. Selective COX-2 inhibitor, NS-398, inhibits the replicative senescence of cultured dermal fibroblasts. Mech Ageing Dev 2004;125:359-366.
123. Herrmann G, et al. Psoralen photoactivation promotes morphological and functional changes in fibroblasts in vitro reminiscent of cellular senescence. J Cell Sci 1998;111:759-767.
124. Shelton DN, Chang E, Whittier PS, Choi D, Funk WD. Microarray analysis of replicative senescence. Curr Biol 1999;9:939-945.
125. Effros RB, Dagarag M, Valenzuela HF. In vitro senescence of immune cells. Exp Gerontol 2003;38:1243-1249.