Naive T Cell Maintenance and Function in Human Aging

Thompson, 2003, Mortality associated with influenza and respiratory syncytial virus in the United States., JAMA, 289, 179, 10.1001/jama.289.2.179

Levin, 2012, Immune senescence and vaccines to prevent herpes zoster in older persons., Curr. Opin. Immunol., 24, 494, 10.1016/j.coi.2012.06.002

Fulop, 2011, Aging, immunity, and cancer., Discov. Med., 11, 537

Morrisette-Thomas, 2014, Inflamm-aging does not simply reflect increases in pro-inflammatory markers., Mech. Ageing Dev., 139, 49, 10.1016/j.mad.2014.06.005

Howcroft, 2013, The role of inflammation in age-related disease., Aging (Albany, N.Y. Online), 5, 84

Franceschi, 2014, Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases., J. Gerontol. A Biol. Sci. Med. Sci., 69, S4, 10.1093/gerona/glu057

Goronzy, 2013, The janus head of T cell aging—autoimmunity and immunodeficiency., Front. Immunol., 4, 131, 10.3389/fimmu.2013.00131

Goronzy, 2012, Immune aging and autoimmunity., Cell. Mol. Life Sci., 69, 1615, 10.1007/s00018-012-0970-0

López-Otín, 2013, The hallmarks of aging., Cell, 153, 1194, 10.1016/j.cell.2013.05.039

Shaw, 2013, Age-dependent dysregulation of innate immunity., Nat. Rev. Immunol., 13, 875, 10.1038/nri3547

Kogut, 2012, B cell maintenance and function in aging., Semin. Immunol., 24, 342, 10.1016/j.smim.2012.04.004

Goronzy, 2013, Understanding immunosenescence to improve responses to vaccines., Nat. Immunol., 14, 428, 10.1038/ni.2588

Montecino-Rodriguez, 2013, Causes, consequences, and reversal of immune system aging., J. Clin. Invest., 123, 958, 10.1172/JCI64096

Nikolich-Žugich, 2014, Aging of the T cell compartment in mice and humans: from no naive expectations to foggy memories., J. Immunol., 193, 2622, 10.4049/jimmunol.1401174

Cheung, 2013, Molecular regulation of stem cell quiescence., Nat. Rev. Mol. Cell Biol., 14, 329, 10.1038/nrm3591

Chinn, 2012, Changes in primary lymphoid organs with aging., Semin. Immunol., 24, 309, 10.1016/j.smim.2012.04.005

Palmer, 2013, The effect of age on thymic function., Front. Immunol., 4, 316, 10.3389/fimmu.2013.00316

Blackman, 2011, The narrowing of the CD8 T cell repertoire in old age., Curr. Opin. Immunol., 23, 537, 10.1016/j.coi.2011.05.005

Hale, 2006, Thymic output in aged mice., Proc. Natl. Acad. Sci. USA, 103, 8447, 10.1073/pnas.0601040103

Qi, 2014, Mechanisms shaping the naïve T cell repertoire in the elderly—thymic involution or peripheral homeostatic proliferation?, Exp. Gerontol., 54, 71, 10.1016/j.exger.2014.01.005

den Braber, 2012, Maintenance of peripheral naive T cells is sustained by thymus output in mice but not humans., Immunity, 36, 288, 10.1016/j.immuni.2012.02.006

Sauce, 2009, Evidence of premature immune aging in patients thymectomized during early childhood., J. Clin. Invest., 119, 3070, 10.1172/JCI39269

Wertheimer, 2014, Aging and cytomegalovirus infection differentially and jointly affect distinct circulating T cell subsets in humans., J. Immunol., 192, 2143, 10.4049/jimmunol.1301721

De Boer, 2013, Quantifying T lymphocyte turnover., J. Theor. Biol., 327, 45, 10.1016/j.jtbi.2012.12.025

Wallace, 2004, Direct measurement of T cell subset kinetics in vivo in elderly men and women., J. Immunol., 173, 1787, 10.4049/jimmunol.173.3.1787

Westera, 2015, Lymphocyte maintenance during healthy aging requires no substantial alterations in cellular turnover., Aging Cell., 14, 219, 10.1111/acel.12311

Sauce, 2012, Lymphopenia-driven homeostatic regulation of naive T cells in elderly and thymectomized young adults., J. Immunol., 189, 5541, 10.4049/jimmunol.1201235

Naylor, 2005, The influence of age on T cell generation and TCR diversity., J. Immunol., 174, 7446, 10.4049/jimmunol.174.11.7446

Surh, 2008, Homeostasis of naive and memory T cells., Immunity, 29, 848, 10.1016/j.immuni.2008.11.002

Fry, 2005, The many faces of IL-7: from lymphopoiesis to peripheral T cell maintenance., J. Immunol., 174, 6571, 10.4049/jimmunol.174.11.6571

Pekalski, 2013, Postthymic expansion in human CD4 naive T cells defined by expression of functional high-affinity IL-2 receptors., J. Immunol., 190, 2554, 10.4049/jimmunol.1202914

Soares, 1998, IL-7-dependent extrathymic expansion of CD45RA+ T cells enables preservation of a naive repertoire., J. Immunol., 161, 5909, 10.4049/jimmunol.161.11.5909

Kilpatrick, 2008, Homeostasis of the naive CD4+ T cell compartment during aging., J. Immunol., 180, 1499, 10.4049/jimmunol.180.3.1499

Kohler, 2009, Life after the thymus: CD31+ and CD31− human naive CD4+ T-cell subsets., Blood, 113, 769, 10.1182/blood-2008-02-139154

Czesnikiewicz-Guzik, 2008, T cell subset-specific susceptibility to aging., Clin. Immunol., 127, 107, 10.1016/j.clim.2007.12.002

Qi, 2014, Diversity and clonal selection in the human T-cell repertoire., Proc. Natl. Acad. Sci. USA, 111, 13139, 10.1073/pnas.1409155111

Sprent, 2011, Normal T cell homeostasis: the conversion of naive cells into memory-phenotype cells., Nat. Immunol., 12, 478, 10.1038/ni.2018

Renkema, 2014, Two separate defects affecting true naive or virtual memory T cell precursors combine to reduce naive T cell responses with aging., J. Immunol., 192, 151, 10.4049/jimmunol.1301453

Reynolds, 2013, Mathematical model of naive T cell division and survival IL-7 thresholds., Front. Immunol., 4, 434, 10.3389/fimmu.2013.00434

Cheng, 2000, Hematopoietic stem cell quiescence maintained by p21cip1/waf1., Science, 287, 1804, 10.1126/science.287.5459.1804

Thome, 2014, Spatial map of human T cell compartmentalization and maintenance over decades of life., Cell, 159, 814, 10.1016/j.cell.2014.10.026

Schönland, 2003, Homeostatic control of T-cell generation in neonates., Blood, 102, 1428, 10.1182/blood-2002-11-3591

Johnson, 2012, Peripheral selection rather than thymic involution explains sudden contraction in naive CD4 T-cell diversity with age., Proc. Natl. Acad. Sci. USA, 109, 21432, 10.1073/pnas.1209283110

Warren, 2011, Exhaustive T-cell repertoire sequencing of human peripheral blood samples reveals signatures of antigen selection and a directly measured repertoire size of at least 1 million clonotypes., Genome Res., 21, 790, 10.1101/gr.115428.110

Robins, 2009, Comprehensive assessment of T-cell receptor β-chain diversity in αβ T cells., Blood, 114, 4099, 10.1182/blood-2009-04-217604

Britanova, 2014, Age-related decrease in TCR repertoire diversity measured with deep and normalized sequence profiling., J. Immunol., 192, 2689, 10.4049/jimmunol.1302064

Rudd, 2011, Nonrandom attrition of the naive CD8+ T-cell pool with aging governed by T-cell receptor:pMHC interactions., Proc. Natl. Acad. Sci. USA, 108, 13694, 10.1073/pnas.1107594108

McMichael, 1998, The original sin of killer T cells., Nature, 394, 421, 10.1038/28738

Johnson, 2014, A population biological approach to understanding the maintenance and loss of the T-cell repertoire during aging., Immunology, 142, 167, 10.1111/imm.12244

Lin, 2015, Age-associated telomere attrition of lymphocytes in vivo is co-ordinated with changes in telomerase activity, composition of lymphocyte subsets and health conditions., Clin. Sci., 128, 367, 10.1042/CS20140481

Lord, 2002, Telomere-based therapy for immunosenescence., Trends Immunol., 23, 175, 10.1016/S1471-4906(02)02170-1

Weng, 1995, Human naive and memory T lymphocytes differ in telomeric length and replicative potential., Proc. Natl. Acad. Sci. USA, 92, 11091, 10.1073/pnas.92.24.11091

Sfeir, 2012, Removal of shelterin reveals the telomere end-protection problem., Science, 336, 593, 10.1126/science.1218498

Moskalev, 2013, The role of DNA damage and repair in aging through the prism of Koch-like criteria., Ageing Res. Rev., 12, 661, 10.1016/j.arr.2012.02.001

Cavanagh, 2012, Chronic inflammation and aging: DNA damage tips the balance., Curr. Opin. Immunol., 24, 488, 10.1016/j.coi.2012.04.003

Burtner, 2010, Progeria syndromes and ageing: what is the connection?, Nat. Rev. Mol. Cell Biol., 11, 567, 10.1038/nrm2944

Fujii, 2009, Telomerase insufficiency in rheumatoid arthritis., Proc. Natl. Acad. Sci. USA, 106, 4360, 10.1073/pnas.0811332106

Shao, 2009, Deficiency of the DNA repair enzyme ATM in rheumatoid arthritis., J. Exp. Med., 206, 1435, 10.1084/jem.20082251

Weyand, 2009, Rejuvenating the immune system in rheumatoid arthritis., Nat. Rev. Rheumatol., 5, 583, 10.1038/nrrheum.2009.180

Hohensinner, 2011, Telomere dysfunction, autoimmunity and aging., Aging Dis., 2, 524

Park, 2011, Mitochondrial DNA mutations in disease and aging., J. Cell Biol., 193, 809, 10.1083/jcb.201010024

Ross, 2002, Mitochondrial DNA damage in lymphocytes: a role in immunosenescence?, Exp. Gerontol., 37, 329, 10.1016/S0531-5565(01)00200-5

Sahin, 2011, Telomere dysfunction induces metabolic and mitochondrial compromise., Nature, 470, 359, 10.1038/nature09787

Sahin, 2010, Linking functional decline of telomeres, mitochondria and stem cells during ageing., Nature, 464, 520, 10.1038/nature08982

Fontana, 2010, Extending healthy life span—from yeast to humans., Science, 328, 321, 10.1126/science.1172539

MacIver, 2013, Metabolic regulation of T lymphocytes., Annu. Rev. Immunol., 31, 259, 10.1146/annurev-immunol-032712-095956

Pollizzi, 2014, Integrating canonical and metabolic signalling programmes in the regulation of T cell responses., Nat. Rev. Immunol., 14, 435, 10.1038/nri3701

Xu, 2014, Autophagy is essential for effector CD8+ T cell survival and memory formation., Nat. Immunol., 15, 1152, 10.1038/ni.3025

Valdor, 2014, Chaperone-mediated autophagy regulates T cell responses through targeted degradation of negative regulators of T cell activation., Nat. Immunol., 15, 1046, 10.1038/ni.3003

Taub, 2013, Distinct energy requirements for human memory CD4 T-cell homeostatic functions., FASEB J., 27, 342, 10.1096/fj.12-217620

Yu, 2012, Signal inhibition by the dual-specific phosphatase 4 impairs T cell-dependent B-cell responses with age., Proc. Natl. Acad. Sci. USA, 109, E879, 10.1073/pnas.1109797109

Henson, 2014, p38 signaling inhibits mTORC1-independent autophagy in senescent human CD8+ T cells., J. Clin. Invest., 124, 4004, 10.1172/JCI75051

Tchkonia, 2013, Cellular senescence and the senescent secretory phenotype: therapeutic opportunities., J. Clin. Invest., 123, 966, 10.1172/JCI64098

Sharpless, 1999, The INK4A/ARF locus and its two gene products., Curr. Opin. Genet. Dev., 9, 22, 10.1016/S0959-437X(99)80004-5

Sperka, 2012, DNA damage checkpoints in stem cells, ageing and cancer., Nat. Rev. Mol. Cell Biol., 13, 579, 10.1038/nrm3420

Coppé, 2011, Tumor suppressor and aging biomarker p16INK4a induces cellular senescence without the associated inflammatory secretory phenotype., J. Biol. Chem., 286, 36396, 10.1074/jbc.M111.257071

Kim, 2006, The regulation of INK4/ARF in cancer and aging., Cell, 127, 265, 10.1016/j.cell.2006.10.003

Liu, 2009, Expression of p16INK4a in peripheral blood T-cells is a biomarker of human aging., Aging Cell, 8, 439, 10.1111/j.1474-9726.2009.00489.x

Migliaccio, 2006, Distinct mechanisms control human naive and antigen-experienced CD8+ T lymphocyte proliferation., J. Immunol., 176, 2173, 10.4049/jimmunol.176.4.2173

Weng, 2009, CD28− T cells: their role in the age-associated decline of immune function., Trends Immunol., 30, 306, 10.1016/j.it.2009.03.013

Wallace, 2011, Human cytomegalovirus-specific CD8+ T-cell expansions contain long-lived cells that retain functional capacity in both young and elderly subjects., Immunology, 132, 27, 10.1111/j.1365-2567.2010.03334.x

Akbar, 2011, Are senescence and exhaustion intertwined or unrelated processes that compromise immunity?, Nat. Rev. Immunol., 11, 289, 10.1038/nri2959

Wang, 2012, A differentiation checkpoint limits hematopoietic stem cell self-renewal in response to DNA damage., Cell, 148, 1001, 10.1016/j.cell.2012.01.040

Su, 2013, Virus-specific CD4+ memory-phenotype T cells are abundant in unexposed adults., Immunity, 38, 373, 10.1016/j.immuni.2012.10.021

Chiu, 2013, Cutting edge: central memory CD8 T cells in aged mice are virtual memory cells., J. Immunol., 191, 5793, 10.4049/jimmunol.1302509

Haluszczak, 2009, The antigen-specific CD8+ T cell repertoire in unimmunized mice includes memory phenotype cells bearing markers of homeostatic expansion., J. Exp. Med., 206, 435, 10.1084/jem.20081829

Chen, 2013, T cell aging: a review of the transcriptional changes determined from genome-wide analysis., Front. Immunol., 4, 121, 10.3389/fimmu.2013.00121

Reynolds, 2014, Age-related variations in the methylome associated with gene expression in human monocytes and T cells., Nat. Commun., 5, 5366, 10.1038/ncomms6366

Goronzy, 2012, Signaling pathways in aged T cells—a reflection of T cell differentiation, cell senescence and host environment., Semin. Immunol., 24, 365, 10.1016/j.smim.2012.04.003

Li, 2012, Decline in miR-181a expression with age impairs T cell receptor sensitivity by increasing DUSP6 activity., Nat. Med., 18, 1518, 10.1038/nm.2963

Li, 2007, miR-181a is an intrinsic modulator of T cell sensitivity and selection., Cell, 129, 147, 10.1016/j.cell.2007.03.008

Adachi, 2011, T-cell receptor ligation induces distinct signaling pathways in naive vs. antigen-experienced T cells., Proc. Natl. Acad. Sci. USA, 108, 1549, 10.1073/pnas.1017340108

Monticelli, 2013, MicroRNAs in T helper cell differentiation and plasticity., Semin. Immunol., 25, 291, 10.1016/j.smim.2013.10.015