Abstract
Like other somatic cells, human T lymphocytes have a finite replicative capacity in vitro, and, by implication and consistent with the limited data available, in vivo as well. An accumulation of dysfunctional T cells may be detrimental under conditions of chronic antigenic stress (chronic infection, cancer, autoimmunity). Using T cells from young donors to model the process of T cell clonal expansion in vitro under these conditions reveals age-associated increasing levels of oxidative DNA damage and microsatellite instability (MSI), coupled with decreasing DNA repair capacity, telomerase induction and telomere length, decreased levels of expression of the T cell costimulator CD28 and consequently reduced secretion of the T cell growth factor interleukin-2 (IL-2). However, data from similar experiments using T cell clones (TCCs) derived from extremely healthy very elderly donors ("successfully aged") indicate that DNA repair is better maintained, MSI less prevalent, and (already short) telomere lengths are maintained. Nonetheless, oxidative DNA damage is seen to the same extent, and clonal longevity is also similar in these clones. DNA damage levels are reduced by culture in 5% oxygen, but longevity is not improved. This may be ...Continue Reading
References
Nov 1, 1996·Experimental Gerontology·G PawelecI Beckman
Feb 26, 1998·Immunological Reviews·G PawelecM Adibzadeh
Apr 10, 1999·Mechanisms of Ageing and Development·D V RaoG L Jones
Oct 18, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·E HooijbergH Spits
Oct 25, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M MigliaccioM Nabholz
Jan 5, 2002·Experimental Gerontology·Graham PawelecRafael Solana
Jan 5, 2002·Experimental Gerontology·Anders WikbyFrederick Ferguson
Jun 28, 2002·Nucleic Acids Research·Li LiuEric B Kmiec
Jul 10, 2002·Trends in Immunology·Graham PawelecCalogero Caruso
Sep 27, 2002·The Journal of Biological Chemistry·Abbe N VallejoJörg J Goronzy
Oct 24, 2002·Blood·David VoehringerHanspeter Pircher
Dec 17, 2002·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Hector F Valenzuela, Rita B Effros
Dec 31, 2002·Blood·Kenneth J WarringtonJörg J Goronzy
Mar 21, 2003·Immunology and Allergy Clinics of North America·Graham PawelecAnders Wikby
May 9, 2003·The Journal of Biological Chemistry·Niki ChondrogianniEfstathios S Gonos
Jun 11, 2003·Nature Immunology·Norihiko WatanabeKenneth M Murphy
Aug 14, 2003·Experimental Gerontology·Qin OuyangGraham Pawelec
Citations
Mar 29, 2012·Age·Juan C Conde-PérezprinaMina Königsberg
Apr 9, 2008·Rejuvenation Research·Marco MalavoltaEugenio Mocchegiani
Aug 10, 2010·The Cancer Journal·Cassian Yee
Mar 1, 2006·Immunity & Ageing : I & a·Sonya VastoGraham Pawelec
Mar 23, 2007·Immunity & Ageing : I & a·Sonya VastoGraham Pawelec
May 11, 2005·Immunological Reviews·Rita B EffrosJanice Man
Jun 7, 2005·Cellular Immunology·Stuart RatnerJennifer Oliver
Mar 14, 2007·Cytotherapy·A RöthU Dührsen