Apoptotic capability in ageing T cells

The ageing immune system shows a gradual decline in responsiveness to antigens and tumours due to the emergence of immunosenescence. The main functions of T cells are activation, anergy and apoptosis and these are all affected during ageing. Apoptosis is vital in controlling cell numbers, deleting self-reactive T cells and maintaining immune surveillance. One of the principle instigators of death involves the CD95:CD95-ligand interaction and as T cells age both receptor and ligand levels increase. This view will describe the current knowledge of the apoptotic susceptibility of ageing T cells and evaluate the factors that may affect the apoptotic capability of immunosenescent T cells.

[1]  L. Walker,et al.  Lack of activation induced cell death in human T blasts despite CD95L
up‐regulation: protection from apoptosis by MEK signalling , 1999, Immunology.

[2]  C. Caruso,et al.  Apoptosis and ageing , 1998, Mechanisms of Ageing and Development.

[3]  J. Gribben,et al.  Induction of T cell clonal anergy results in resistance, whereas CD28-mediated costimulation primes for susceptibility to Fas- and Bax-mediated programmed cell death. , 1997, Journal of immunology.

[4]  R. Effros,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 , 1994, Experimental Gerontology.

[5]  R. Whisler,et al.  Age-related reductions in the activation of mitogen-activated protein kinases p44mapk/ERK1 and p42mapk/ERK2 in human T cells stimulated via ligation of the T cell receptor complex. , 1996, Cellular immunology.

[6]  D. Chao,et al.  BCL-2 family: regulators of cell death. , 1998, Annual review of immunology.

[7]  F. Ramsdell,et al.  Differential ability of Th1 and Th2 T cells to express Fas ligand and to undergo activation-induced cell death. , 1994, International immunology.

[8]  C. Thompson,et al.  Bcl-x(L) can inhibit apoptosis in cells that have undergone Fas-induced protease activation. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[9]  L. Walker,et al.  Activation of human T cells with superantigen (staphylococcal enterotoxin B) and CD28 confers resistance to apoptosis via CD95. , 1998, Journal of immunology.

[10]  Gupta,et al.  Increased activity of caspase 3 and caspase 8 in anti‐Fas‐induced apoptosis in lymphocytes from ageing humans , 1999, Clinical and experimental immunology.

[11]  Takashi Suda,et al.  Molecular cloning and expression of the fas ligand, a novel member of the tumor necrosis factor family , 1993, Cell.

[12]  M. Martínez-Lorenzo,et al.  Release of preformed Fas ligand in soluble form is the major factor for activation‐induced death of Jurkat T cells , 1996, Immunology.

[13]  G. Kroemer.  [Mitochondrial control of apoptosis]. , 2001, Bulletin de l'Academie nationale de medecine.

[14]  V. Sánchez-Margalet,et al.  Protein kinase C activation promotes cell survival in mature lymphocytes prone to apoptosis. , 1994, Biochemical pharmacology.

[15]  M. Little,et al.  Apoptosis of a human melanoma cell line specifically induced by membrane-bound single-chain antibodies. , 1999, Journal of immunology.

[16]  O. Janssen,et al.  Induction of activation-driven death (apoptosis) in activated but not resting peripheral blood T cells. , 1993, Journal of immunology.

[17]  M. T. Falta,et al.  Functional subsets within clonally expanded CD8(+) memory T cells in elderly humans. , 2000, Clinical immunology.

[18]  C. Franceschi,et al.  Expansion of cytotoxic CD8+ CD28− T cells in healthy ageing people, including centenarians , 1996, Immunology.

[19]  G. Pawelec,et al.  Long-term culture of monoclonal human T lymphocytes: models for immunosenescence? , 1995, Mechanisms of Ageing and Development.

[20]  G. Pawelec,et al.  Lifespans of T lymphocytes , 1996, Mechanisms of Ageing and Development.

[21]  D. Green,et al.  Unequal Death in T Helper Cell (Th)1 and Th2 Effectors: Th1, but not Th2, Effectors Undergo Rapid Fas/FasL-mediated Apoptosis , 1997, The Journal of experimental medicine.

[22]  S. Boutet,et al.  Susceptibility to apoptosis of T lymphocytes from elderly humans is associated with increased in vivo expression of functional Fas receptors , 1997, Mechanisms of Ageing and Development.

[23]  H. Lecoeur,et al.  Differential susceptibility to activation-induced apoptosis among peripheral Th1 subsets: correlation with Bcl-2 expression and consequences for AIDS pathogenesis. , 1998, Journal of immunology.

[24]  G. Pawelec,et al.  T cells and aging. , 1998, Frontiers in bioscience : a journal and virtual library.

[25]  N. Restifo.  Not so Fas: Re-evaluating the mechanisms of immune privilege and tumor escape , 2000, Nature Medicine.

[26]  G. Pawelec,et al.  T cells and aging (update february 1999). , 1999, Frontiers in bioscience : a journal and virtual library.

[27]  T. Miyawaki,et al.  Differential expression of apoptosis-related Fas antigen on lymphocyte subpopulations in human peripheral blood. , 1992, Journal of immunology.

[28]  M. Salmon,et al.  Cellular environments and apoptosis: tissue microenvironments control activated T-cell death. , 1997, Immunology today.

[29]  G. Shearer,et al.  Th1/Th2 changes in aging. , 1997, Mechanisms of ageing and development.

[30]  V. Fadok,et al.  Apoptosis and programmed cell death in immunity. , 1992, Annual review of immunology.

[31]  E. Garrafa,et al.  Generation of CD28− cells from long‐term‐stimulated CD8+CD28+ T cells: a possible mechanism accounting for the increased number of CD8+CD28− T cells in HIV‐1‐infected patients , 1999, Journal of leukocyte biology.

[32]  M. Pahlavani,et al.  Activation of p21ras/MAPK signal transduction molecules decreases with age in mitogen-stimulated T cells from rats. , 1998, Cellular immunology.

[33]  G. Pawelec,et al.  The T cell in the ageing individual 1 This article is based on a presentation to the First International Conference on Aging and Immunology, Bethesda, MD, 16–19 June, 1996. 1 , 1997, Mechanisms of Ageing and Development.

[34]  J. Allison,et al.  The Role of CTLA‐4 in the Regulation and Initiation of T‐Cell Responses , 1996, Immunological reviews.

[35]  C. Smith,et al.  Fas ligand mediates activation-induced cell death in human T lymphocytes , 1995, The Journal of experimental medicine.

[36]  O. Pereira-smith,et al.  Replicative Senescence: Implications for in Vivo Aging and Tumor Suppression , 1996, Science.

[37]  P. Salgame,et al.  Differential ability of T cell subsets to undergo activation-induced cell death. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[38]  G. Pawelec,et al.  Decreased proliferative capacity and increased susceptibility to activation-induced cell death in late-passage human cd4+ tcr2+ cultured T cell clones , 1996, Experimental Gerontology.

[39]  Masashi Narita,et al.  Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC , 1999, Nature.

[40]  S. Aggarwal,et al.  Increased apoptosis of T cell subsets in aging humans: altered expression of Fas (CD95), Fas ligand, Bcl-2, and Bax. , 1998, Journal of immunology.

[41]  P. Linsley,et al.  CD28 engagement and proinflammatory cytokines contribute to T cell expansion and long-term survival in vivo. , 1997, Journal of immunology.

[42]  G. Pawelec,et al.  Molecular and cellular basis of immunosenescence , 1998, Mechanisms of Ageing and Development.

[43]  S. Nagata,et al.  Downregulation of Fas ligand by shedding , 1998, Nature Medicine.

[44]  Arul M. Chinnaiyan,et al.  The Receptor for the Cytotoxic Ligand TRAIL , 1997, Science.

[45]  A. Alessandrini,et al.  MEK1 activation rescues Jurkat T cells from Fas-induced apoptosis. , 1999, Cellular immunology.

[46]  C. Weyand,et al.  Functional properties of CD4+CD28− T cells in the aging immune system , 1998, Mechanisms of Ageing and Development.

[47]  G. Pawelec,et al.  Age-related changes in the expression of CD95 (APO1/FAS) on blood lymphocytes☆ , 1999, Experimental Gerontology.

[48]  P. Krammer,et al.  Autocrine T-cell suicide mediated by APO-1/(Fas/CD95) , 1995, Nature.

[49]  T. Griffith,et al.  The role of FasL-induced apoptosis in immune privilege. , 1997, Immunology today.

[50]  C B Harley,et al.  Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes. , 1993, American journal of human genetics.

[51]  Terry Farrah,et al.  The TNF receptor superfamily of cellular and viral proteins: Activation, costimulation, and death , 1994, Cell.

[52]  R. Effros,et al.  Resistance to apoptosis in human CD8+ T cells that reach replicative senescence after multiple rounds of antigen-specific proliferation☆ , 1999, Experimental Gerontology.