• 1
    Borchers AT, Selmi C, Cheema G, Keen CL, Shoenfeld Y, Gershwin ME. Juvenile idiopathic arthritis. Autoimmun Rev 2006; 5: 27998.
  • 2
    Murray KJ, Thompson SD, Glass DN. Pathogenesis of juvenile chronic arthritis: genetic and environmental factors. Arch Dis Child 1997; 77: 5304.
  • 3
    Wedderburn LR, Woo P. Type 1 and type 2 immune response in children: their relevance in juvenile arthritis. Springer Semin Immunopathol 1999; 21: 36174.
  • 4
    Firestein GS. Evolving concepts of rheumatoid arthritis. Nature 2003; 423: 35661.
  • 5
    Linton PJ, Dorshkind K. Age-related changes in lymphocyte development and function. Nat Immunol 2004; 5: 1339.
  • 6
    Goldrath AW. Maintaining the status quo: T-cell homeostasis. Microbes Infect 2002; 4: 53945.
  • 7
    Wagner UG, Koetz K, Weyand CM, Goronzy JJ. Perturbation of the T cell repertoire in rheumatoid arthritis. Proc Natl Acad Sci U S A 1998; 95: 1444752.
  • 8
    Schmidt D, Goronzy JJ, Weyand CM. CD4+CD7CD28 T cells are expanded in rheumatoid arthritis and are characterized by autoreactivity. J Clin Invest 1996; 97: 202737.
  • 9
    Ponchel F, Morgan AW, Bingham SJ, Quinn M, Buch M, Verburg RJ, et al. Dysregulated lymphocyte proliferation and differentiation in patients with rheumatoid arthritis. Blood 2002; 100: 45506.
  • 10
    Bakakos P, Pickard C, Wong WM, Ayre KR, Madden J, Frew AJ, et al. Simultaneous analysis of T cell clonality and cytokine production in rheumatoid arthritis using three-colour flow cytometry. Clin Exp Immunol 2002; 129: 3708.
  • 11
    Fasth AE, Cao D, van Vollenhoven R, Trollmo C, Malmstrom V. CD28nullCD4+ T cells: characterization of an effector memory T-cell population in patients with rheumatoid arthritis. Scand J Immunol 2004; 60: 199208.
  • 12
    Wagner U, Pierer M, Kaltenhauser S, Wilke B, Seidel W, Arnold S, et al. Clonally expanded CD4+CD28null T cells in rheumatoid arthritis use distinct combinations of T cell receptor BV and BJ elements. Eur J Immunol 2003; 33: 7984.
  • 13
    Warrington KJ, Takemure S, Goronzy JJ, Weyand CM. CD4+,CD28− T cells in rheumatoid arthritis patients combine features of the innate and adaptive immune systems. Arthritis Rheum 2001; 44: 1320.
  • 14
    Douek DC, McFarland RD, Keiser PH, Gage EA, Massey JM, Haynes BF, et al. Changes in thymic function with age and during the treatment of HIV infection. Nature 1998; 396: 6905.
  • 15
    Zhang X, Sun S, Hwang I, Tough DF, Sprent J. Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL-15. Immunity 1998; 8: 5919.
  • 16
    Hazenberg MD, Verschuren MC, Hamann D, Miedema F, van Dongen JJ. T cell receptor excision circles as markers for recent thymic emigrants: basic aspects, technical approach, and guidelines for interpretation. J Mol Med 2001; 79: 63195.
  • 17
    Stulnig T, Maczek C, Bock G, Madjic O, Wick G. Reference intervals for human peripheral blood lymphocyte subpopulation from “healthy” young and aged subjects. Int Arch Allergy Immunol 1995; 108: 20510.
  • 18
    Blackburn EH. Structure and function of telomeres. Nature 1991; 350: 56973.
  • 19
    Weng NP, Levine BL, June CH, Hodes RJ. Human naive and memory T lymphocytes differ in telomeric length and replicative potential. Proc Natl Acad Sci U S A 1995; 92: 110914.
  • 20
    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 U S A 2000; 97: 92038.
  • 21
    Honda M, Mengesha E, Albano S, Nichols WS, Wallace DJ, Metzger A, et al. Telomere shortening and decreased replicative potential, contrasted by continued proliferation of telomerase-positive CD8+CD28lo T cells in patients with systemic lupus erythematosus. Clin Immunol 2001; 99: 21121.
  • 22
    Thewissen M, Linsen L, Somers V, Geusens P, Raus J, Stinissen P. Premature immunosenescence in rheumatoid arthritis and multiple sclerosis patients. Ann N Y Acad Sci 2005; 1051: 25562.
  • 23
    Petty RE, Southwood TR, Baum J, Bhettay E, Glass DN, Manners P, et al. Revision of the proposed classification criteria for juvenile idiopathic arthritis: Durban, 1997. J Rheumatol 1998; 25: 19914.
  • 24
    Harris JM, Hazenberg MD, Poulin JF, Higuera-Alhino D, Schmidt D, Gotway M, et al. Multiparameter evaluation of human thymic function: interpretation and caveats. Clin Immunol 2005; 115: 13846.
  • 25
    Koppelstaetter C, Jennings P, Hochegger K, Perco P, Ischia R, Karkoszka H, et al. Effect of tissue fixatives on telomere length determination by quantitative PCR. Mech Ageing Dev 2005; 126: 13313.
  • 26
    Cawthon RM. Telomere measurement by quantitative PCR. Nucleic Acids Res 2002; 30: e47.
  • 27
    Vallejo AN, Weyand CM, Goronzy JJ. T-cell senescence: a culprit of immune abnormalities in chronic inflammation and persistent infection. Trends Mol Med 2004; 10: 11924.
  • 28
    Poulin JF, Viswanathan MN, Harris JM, Komanduri KV, Wieder E, Ringuette N, et al. Direct evidence for thymic function in adult humans. J Exp Med 1999; 190: 47986.
  • 29
    Freitas AA, Rocha B. Population biology of lymphocytes: the flight for survival. Annu Rev Immunol 2000; 18: 83111.
  • 30
    Goldrath AW, Bevan MJ. Low-affinity ligands for the TCR drive proliferation of mature CD8+ T cells in lymphopenic hosts. Immunity 1999; 11: 18390.
  • 31
    Fink PJ, Bevan MJ. Positive selection of thymocytes. Adv Immunol 1995; 59: 99133.
  • 32
    Hazenberg MD, Borghans JA, de Boer RJ, Miedema F. Thymic output: a bad TREC record. Nat Immunol 2003; 4: 979.
  • 33
    Kong FK, Chen CL, Six A, Hockett RD, Cooper MD. T cell receptor gene deletion circles identify recent thymic emigrants in the peripheral T cell pool. Proc Natl Acad Sci U S A 1999; 96: 153640.
  • 34
    Hazenberg MD, Otto SA, Cohen Stuart JW, Verschuren MC, Borleffs JC, Boucher CA, et al. Increased cell division but not thymic dysfunction rapidly affects the T cell receptor excision circle content of the naïve T cell population in HIV-1 infection. Nat Med 2000; 6: 103642.
  • 35
    Goronzy JJ, Weyand CM. Rheumatoid arthritis. Immunol Rev 2005; 204: 5573.
  • 36
    Goronzy JJ, Fujii H, Weyand CM. Telomeres, immune aging and autoimmunity. Exp Gerontol 2006; 41: 24651.
  • 37
    Schonland SO, Lopez C, Widmann T, Zimmer J, Bryl E, Goronzy JJ, et al. Premature telomeric loss in rheumatoid arthritis is genetically determined and involves both myeloid and lymphoid cell lineages. Proc Natl Acad Sci U S A 2003; 100: 134716.
  • 38
    Jameson SC. Maintaining the norm: T-cell homeostasis. Nat Rev Immunol 2002; 2: 54756.
  • 39
    Goldrath AW, Bevan MJ. Selecting and maintaining a diverse T-cell repertoire. Nature 1999; 402: 25562.
  • 40
    Goronzy JJ, Weyand CM. Thymic function and peripheral T cell homeostasis in rheumatoid arthritis. Trends Immunol 2001; 22: 2515.
  • 41
    Grubeck-Loebenstein B, Wick G. The aging of the immune system. Adv Immunol 2002; 80: 24384.
  • 42
    Weyand CM, Fulbright JW, Goronzy JJ. Immunosenescence, autoimmunity, and rheumatoid arthritis. Exp Gerontol 2003; 38: 83341.
  • 43
    Effros RB. Loss of CD28 expression on T lymphocytes: a marker of replicative senescence. Dev Comp Immunol 1997; 21: 4718.
  • 44
    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: 811929.
  • 45
    Weyand CM, Brandes JC, Schmidt D, Fulbright JW, Goronzy JJ. Functional properties of CD4+ CD28− T cells in the aging immune system. Mech Ageing Dev 1998; 102: 13147.
  • 46
    Chamberlain WD, Falta MT, Kotzin BL. Functional subsets within clonally expanded CD8+ memory T cells in elderly humans. Clin Immunol 2000; 94: 16072.
  • 47
    Fitzgerald JE, Ricalton NS, Meyer AC, West SG, Kaplan H, Behrendt C, et al. Analysis of clonal CD8+ T cell expansions in normal individuals and patients with rheumatoid arthritis. J Immunol 1995; 154: 353847.
  • 48
    Martens PB, Goronzy JJ, Schaid D, Weyand CM. Expansion of unusual CD4+ T cells in severe rheumatoid arthritis. Arthritis Rheum 1997; 40: 110614.
  • 49
    Prelog M. Aging of the immune system: a risk factor for autoimmunity? Autoimmun Rev 2006; 5: 1369.