Cited by 134T-cell and B-cell ImmunologyGenetics, Aging, and Longevity in Model OrganismsImmune Response and Inflammation

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Signaling pathways in aged T cells – A reflection of T cell differentiation, cell senescence and host environment

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Goronzy, Jörg J., Li, Guangjin, Yu, Mingcan, Weyand, Cornelia M.·2012·Seminars in Immunology

DOI 10.1016/j.smim.2012.04.003PMC PMC3435478

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Abstract

With increasing age, the ability of the immune system to protect against new antigenic challenges or to control chronic infections erodes. Decline in thymic function and cumulating antigenic experiences of acute and chronic infections threaten T cell homeostasis, but insufficiently explain the failing immune competence and the increased susceptibility for autoimmunity. Alterations in signaling pathways in the aging T cells account for many of the age-related defects. Signaling threshold calibrations seen with aging frequently built on mechanisms that are operational in T cell development and T cell differentiation or are adaptations to the changing environment in the aging host. Age-related changes in transcription of receptors and signaling molecules shift the balance towards inhibitory pathways, most dominantly seen in CD8 T cells and to a lesser degree in CD4 T cells. Prominent examples are the expression of negative regulatory receptors of the CD28 and the TNF receptor superfamilies as well the expression of various cytoplasmic and nuclear dual-specific phosphatases.

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Mitochondria, Oxidants, and Aging
Balaban, R. S., Nemoto, S., & Finkel, T. (2005) · Cell · doi:10.1016/j.cell.2005.02.001 · Cited by 4,388
Mortality Associated With Influenza and Respiratory Syncytial Virus in the United States
Thompson, W. W., Shay, D. K., Weintraub, E., Brammer, L., Cox, N., Anderson, L. J., & Fukuda, K. (2003) · JAMA · doi:10.1001/jama.289.2.179 · Cited by 3,673
Microbial translocation is a cause of systemic immune activation in chronic HIV infection
Brenchley, J. M., Price, D. A., Schacker, T. W., Asher, T. E., Silvestri, G., Rao, S., Kazzaz, Z., Bornstein, E., Lambotte, O., Altmann, D., et al. (2006) · Nature Medicine · doi:10.1038/nm1511 · Cited by 3,559
AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity
Cantó, C., Gerhart-Hines, Z., Feige, J. N., Lagouge, M., Noriega, L., Milne, J. C., Elliott, P. J., Puigserver, P., & Auwerx, J. (2009) · Nature · doi:10.1038/nature07813 · Cited by 3,300
Signal transduction by reactive oxygen species
Finkel, T. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201102095 · Cited by 2,322
AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy
Hardie, D. G. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2249 · Cited by 2,261
Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
Wherry, E. J., Ha, S.-J., Kaech, S. M., Haining, W. N., Sarkar, S., Kalia, V., Subramaniam, S., Blattman, J. N., Barber, D. L., & Ahmed, R. (2007) · Immunity · doi:10.1016/j.immuni.2007.09.006 · Cited by 2,103
Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
Wherry, E. J., Ha, S., Kaech, S. M., Haining, W. N., Sarkar, S., Kalia, V., Subramaniam, S., Blattman, J. N., Barber, D. L., & Ahmed, R. (2007) · Immunity · doi:10.1016/j.immuni.2007.11.006 · Cited by 1,355
Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage
Falck, J., Coates, J., & Jackson, S. P. (2005) · Nature · doi:10.1038/nature03442 · Cited by 1,304
miR-181a Is an Intrinsic Modulator of T Cell Sensitivity and Selection
Li, Q.-J., Chau, J., Ebert, P. J. R., Sylvester, G., Min, H., Liu, G., Braich, R. S., Manoharan, M., Soutschek, J., Skare, P., et al. (2007) · Cell · doi:10.1016/j.cell.2007.03.008 · Cited by 1,165
Inflammatory mediators in the elderly
Krabbe, K. S., Pedersen, M., & Bruunsgaard, H. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2004.01.009 · Cited by 928
Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1
Denchi, E. L., & de Lange, T. (2007) · Nature · doi:10.1038/nature06065 · Cited by 880
Cytokine Signaling Modules in Inflammatory Responses
O’Shea, J. J., & Murray, P. J. (2008) · Immunity · doi:10.1016/j.immuni.2008.03.002 · Cited by 833
SOCS Proteins: Negative Regulators of Cytokine Signaling
Krebs, D. L., & Hilton, D. J. (2001) · Stem Cells · doi:10.1634/stemcells.19-5-378 · Cited by 826
The Influence of Age on T Cell Generation and TCR Diversity
Naylor, K., Li, G., Vallejo, A. N., Lee, W.-W., Koetz, K., Bryl, E., Witkowski, J., Fulbright, J., Weyand, C. M., & Goronzy, J. J. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.11.7446 · Cited by 802
Self-citation
Immune reconstitution inflammatory syndrome in patients starting antiretroviral therapy for HIV infection: a systematic review and meta-analysis
Müller, M. C. M., Wandel, S., Colebunders, R., Attia, S. L., Furrer, H., & Egger, M. (2010) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(10)70026-8 · Cited by 762
Homeostatic expansion of T cells during immune insufficiency generates autoimmunity.
King, C., Ilic, A., Koelsch, K., & Sarvetnick, N. (2004) · Cell · doi:10.1016/s0092-8674(04)00335-6 · Cited by 747
Aging of the innate immune system
Shaw, A. C., Joshi, S., Greenwood, H., Panda, A., & Lord, J. M. (2010) · Current Opinion in Immunology · doi:10.1016/j.coi.2010.05.003 · Cited by 647
Effectiveness of Influenza Vaccine in the Community-Dwelling Elderly
Nichol, K. L., Nordin, J. D., Nelson, D. B., Mullooly, J. P., & Hak, E. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa070844 · Cited by 647
CD28− T cells: their role in the age-associated decline of immune function
Weng, N., Akbar, A. N., & Goronzy, J. J. (2009) · Trends in Immunology · doi:10.1016/j.it.2009.03.013 · Cited by 630
Self-citation
Efficacy and effectiveness of influenza vaccines in elderly people: a systematic review
Jefferson, T., Rivetti, D., Rivetti, A., Rudin, M., Di Pietrantonj, C., & Demicheli, V (2005) · The Lancet · doi:10.1016/s0140-6736(05)67339-4 · Cited by 601
Vitamin D controls T cell antigen receptor signaling and activation of human T cells
von Essen, M. R., Kongsbak‐Wismann, M., Schjerling, P., Ølgaard, K., Ødum, N., & Geisler, C. (2010) · Nature Immunology · doi:10.1038/ni.1851 · Cited by 547
T cell subset-specific susceptibility to aging
Czesnikiewicz-Guzik, M., Lee, W.-W., Cui, D., Hiruma, Y., Lamar, D. L., Yang, Z.-Z., Ouslander, J. G., Weyand, C. M., & Goronzy, J. J. (2008) · Clinical Immunology · doi:10.1016/j.clim.2007.12.002 · Cited by 478
Self-citation
Aging of the Immune System: How Much Can the Adaptive Immune System Adapt?
Weng, N. (2006) · Immunity · doi:10.1016/j.immuni.2006.05.001 · Cited by 476
Dynamic regulation of miRNA expression in ordered stages of cellular developmentPreprint
Neilson, J. R., Zheng, G. X. Y., Burge, C. B., & Sharp, P. A. (2007) · Genes & Development · doi:10.1101/gad.1522907 · Cited by 476
Are senescence and exhaustion intertwined or unrelated processes that compromise immunity?
Akbar, A. N., & Henson, S. M. (2011) · Nature Reviews Immunology · doi:10.1038/nri2959 · Cited by 474
AMP-activated protein kinase and its downstream transcriptional pathways
Cantó, C., & Auwerx, J. (2010) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-010-0454-z · Cited by 421
Negative signaling by inhibitory receptors: the NK cell paradigm
Long, E. O. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00660.x · Cited by 381
Signaling mechanisms through gp130: A model of the cytokine system
Hirano, T., Nakajima, K., & Hibi, M. (1997) · Cytokine & Growth Factor Reviews · doi:10.1016/s1359-6101(98)80005-1 · Cited by 375
Lack of proliferative capacity of human effector and memory T cells expressing killer cell lectinlike receptor G1 (KLRG1)
Voehringer, D., Koschella, M., & Pircher, H. (2002) · Blood · doi:10.1182/blood-2002-02-0657 · Cited by 352
T cell activation requires mitochondrial translocation to the immunological synapse
Quintana, A., Schwindling, C., Wenning, A. S., Becherer, U., Rettig, J., Schwarz, E. C., & Hoth, M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703126104 · Cited by 347
The ATM protein kinase and cellular redox signaling: beyond the DNA damage response
Ditch, S., & Paull, T. T. (2011) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2011.10.002 · Cited by 333
Free radicals and senescence
Lu, T., & Finkel, T. (2008) · Experimental Cell Research · doi:10.1016/j.yexcr.2008.01.011 · Cited by 327
The DNA Damage Machinery and Homologous Recombination Pathway Act Consecutively to Protect Human Telomeres
Verdún, R. E., & Karlseder, J. (2006) · Cell · doi:10.1016/j.cell.2006.09.034 · Cited by 326
Superantigen-Dependent, Cell-Mediated Cytotoxicity Inhibited by MHC Class I Receptors on T Lymphocytes
Phillips, J. H., Gumperz, J. E., Parham, P., & Lanier, L. L. (1995) · Science · doi:10.1126/science.7716542 · Cited by 305
Aging, Immunity, and the Varicella–Zoster Virus
Arvin, A. M. (2005) · New England Journal of Medicine · doi:10.1056/nejmp058091 · Cited by 305
Chronic tumor necrosis factor alters T cell responses by attenuating T cell receptor signaling
Cope, A. P., Liblau, R. S., Yang, X.-D., Congia, M., Laudanna, C., Schreiber, R. D., Probert, L., Kollias, G., & McDevitt, H. O. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.9.1573 · Cited by 287
The Jak-Stat Pathway: Cytokine Signalling from the Receptor to the Nucleus
Heim, M. H. (1999) · Journal of Receptors and Signal Transduction · doi:10.3109/10799899909036638 · Cited by 275
Aging and T-cell diversity☆
Goronzy, J. J., Lee, W., & Weyand, C. M. (2007) · Experimental Gerontology · doi:10.1016/j.exger.2006.11.016 · Cited by 269
Self-citation
Regulation of T-cell function by endogenously produced angiotensin II
Hoch, N. E., Guzik, T. J., Chen, W., Deans, T., Maalouf, S., Gratze, P., Weyand, C. M., & Harrison, D. G. (2008) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.90521.2008 · Cited by 265
Self-citation
Down-Regulation of CD28 Expression by TNF-α
Bryl, E., Vallejo, A. N., Weyand, C. M., & Goronzy, J. J. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.6.3231 · Cited by 264
Self-citation
KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells
Henson, S. M., Franzese, O., Macaulay, R., Libri, V., Azevedo, R. I., Kiani-Alikhan, S., Plunkett, F. J., Masters, J. E., Jackson, S., Griffiths, S. J., et al. (2009) · Blood · doi:10.1182/blood-2009-01-199588 · Cited by 262
The mature activating natural killer cell immunologic synapse is formed in distinct stages
Orange, J. S., Harris, K. E., Andzelm, M. M., Valter, M. M., Geha, R. S., & Strominger, J. L. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1835830100 · Cited by 260
Mitochondrial Reactive Oxygen Species Control T Cell Activation by Regulating IL-2 and IL-4 Expression: Mechanism of Ciprofloxacin-Mediated Immunosuppression
Kamiński, M. M., Sauer, S. W., Klemke, C., Süss, D., Okun, J. G., Krammer, P. H., & Gülow, K. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0901662 · Cited by 259
Cytotoxic immunological synapses
Dustin, M. L., & Long, E. O. (2010) · Immunological Reviews · doi:10.1111/j.0105-2896.2010.00904.x · Cited by 259
Phenotype, Function, and Gene Expression Profiles of Programmed Death-1hi CD8 T Cells in Healthy Human Adults
Duraiswamy, J., Ibegbu, C., Masopust, D., Miller, J. D., Araki, K., Doho, G., Tata, P., Sk, G., Zilliox, M. J., Nakaya, H. I., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1001783 · Cited by 246
Vav1 Dephosphorylation by the Tyrosine Phosphatase SHP-1 as a Mechanism for Inhibition of Cellular Cytotoxicity
Stebbins, C. C., Watzl, C., Billadeau, D. D., Leibson, P. J., Burshtyn, D. N., & Long, E. O. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.17.6291-6299.2003 · Cited by 245
Memory T cell homeostasis and senescence during aging
Akbar, A. N., & Fletcher, J. M. (2005) · Current Opinion in Immunology · doi:10.1016/j.coi.2005.07.019 · Cited by 231
Zinc transporter ZIP8 (SLC39A8) and zinc influence IFN-γ expression in activated human T cells
Aydemir, T. B., Liuzzi, J. P., McClellan, S., & Cousins, R. J. (2009) · Journal of Leukocyte Biology · doi:10.1189/jlb.1208759 · Cited by 229
Suppressors of cytokine signalling: SOCS
Larsen, L., & Röpke, C. (2002) · Apmis · doi:10.1034/j.1600-0463.2002.1101201.x · Cited by 219
The Vav–Rac1 Pathway in Cytotoxic Lymphocytes Regulates the Generation of Cell-mediated Killing
Billadeau, D. D., Brumbaugh, K. M., Dick, C. J., Schoon, R. A., Bustelo, X. R., & Leibson, P. J. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.3.549 · Cited by 181
Spatial Organization of Signal Transduction Molecules in the NK Cell Immune Synapses During MHC Class I-Regulated Noncytolytic and Cytolytic Interactions
Vyas, Y. M., Mehta, K. M., Morgan, M. M., Maniar, H. S., Butros, L. J., Jung, S., Burkhardt, J. K., & Dupont, B. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.8.4358 · Cited by 180
Aging-related Deficiency of CD28 Expression in CD4+ T Cells Is Associated with the Loss of Gene-specific Nuclear Factor Binding Activity
Vallejo, A. N., Nestel, A. R., Schirmer, M., Weyand, C. M., & Goronzy, J. J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.14.8119 · Cited by 179
Self-citation
Loss of CD28 expression on T lymphocytes: A marker of replicative senescence
Effros, R. B. (1997) · Developmental & Comparative Immunology · doi:10.1016/s0145-305x(97)00027-x · Cited by 175
Regulation of T cell receptor signaling by activation-induced zinc influx
Yu, M., Lee, W., Tomar, D., Pryshchep, S., Cześnikiewicz‐Guzik, M., Lamar, D. L., Li, G., Singh, K., Tian, L., Weyand, C. M., et al. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20100031 · Cited by 172
Self-citation
T Cell Receptor Stimulation, Reactive Oxygen Species, and Cell Signaling
Williams, M. S., & Kwon, J. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.05.029 · Cited by 167
Inflammation, Coagulation, and the Pathway to Frailty
Kanapuru, B., & Ershler, W. B. (2009) · The American Journal of Medicine · doi:10.1016/j.amjmed.2009.01.030 · Cited by 167
Deficiency of the DNA repair enzyme ATM in rheumatoid arthritis.
Shao, L., Fujii, H., Colmegna, I., Oishi, H., Goronzy, J. J., & Weyand, C. M. (2009) · Journal of Experimental Medicine · doi:10.1084/jem.20082251 · Cited by 159
Self-citation
Early activation defects in T lymphocytes from aged mice
Miller, R. A., Gorcia, G., Kirk, C. J., & Witkowski, J. M. (1997) · Immunological Reviews · doi:10.1111/j.1600-065x.1997.tb01029.x · Cited by 146
The CD85/LIR-1/ILT2 Inhibitory Receptor Is Expressed by All Human T Lymphocytes and Down-Regulates Their Functions
Saverino, D., Fabbi, M., Ghiotto, F., Merlo, A. C., Bruno, S., Zarcone, D., Tenca, C., Tiso, M., Santoro, G., Anastasi, G., et al. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.7.3742 · Cited by 145
Ig-Like Transcript 2 (ILT2)/Leukocyte Ig-Like Receptor 1 (LIR1) Inhibits TCR Signaling and Actin Cytoskeleton Reorganization
Dietrich, J., Cella, M., & Colonna, M. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.4.2514 · Cited by 143
Partial restoration of T‐cell function in aged mice by in vitro blockade of the PD‐1/ PD‐L1 pathway
Lages, C. S., Lewkowich, I. P., Sproles, A. A., Wills-Karp, M. A., & Chougnet, C. A. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00611.x · Cited by 141
Displacement of Linker for Activation of T Cells from the Plasma Membrane Due to Redox Balance Alterations Results in Hyporesponsiveness of Synovial Fluid T Lymphocytes in Rheumatoid Arthritis
Gringhuis, S. I., Leow, A., der Voort, E. A. M. P.-V., Remans, P. H. J., Breedveld, F. C., & Verweij, C. L. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.4.2170 · Cited by 140
Will telomere erosion lead to a loss of T-cell memory?
Akbar, A. N., Beverley, P. C. L., & Salmon, M. (2004) · Nature Reviews Immunology · doi:10.1038/nri1440 · Cited by 135
A Balance between Positive and Negative Signals in Cytotoxic Lymphocytes Regulates the Polarization of Lipid Rafts during the Development of Cell-Mediated Killing
Lou, Z., Jevremović, D., Billadeau, D. D., & Leibson, P. J. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.191.2.347 · Cited by 135
The role of the T cell in age-related inflammation
Macaulay, R., Akbar, A. N., & Henson, S. M. (2012) · AGE · doi:10.1007/s11357-012-9381-2 · Cited by 130
Dramatic increase in naïve T cell turnover is linked to loss of naïve T cells from old primates
Čičin-Šain, L., Messaoudi, I., Park, B., Currier, N., Planer, S., Fischer, M., Tackitt, S., Nikolich-Žugich, D., Legasse, A., Axthelm, M. K., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705905104 · Cited by 129
CD4 T cells, lymphopenia, and IL-7 in a multistep pathway to autoimmunity
Calzascia, T., Pellegrini, M., Lin, A., Garza, K. M., Elford, A. R., Shahinian, A., Ohashi, P. S., & Mak, T. W. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0712135105 · Cited by 129
Differential role of lipid rafts in the functions of CD4+ and CD8+ human T lymphocytes with aging
Larbi, A., Dupuis, G., Khalil, A., Douziech, N., Fortin, C., & Fülöp, T. (2006) · Cellular Signalling · doi:10.1016/j.cellsig.2005.08.016 · Cited by 126
Age-associated alterations in the recruitment of signal-transduction proteins to lipid rafts in human T lymphocytes
Larbi, A., Douziech, N., Dupuis, G., Khalil, A., Pelletier, H., Guérard, K., & Fülöp, T. (2003) · Journal of Leukocyte Biology · doi:10.1189/jlb.0703319 · Cited by 126
Stepwise cytoskeletal polarization as a series of checkpoints in innate but not adaptive cytolytic killing
Wülfing, C., Purtic, B., Klem, J., & Schatzle, J. D. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1336920100 · Cited by 123
The Role of the Nonhomologous End-Joining DNA Double-Strand Break Repair Pathway in Telomere Biology
Říha, K., Heacock, M. L., & Shippen, D. E. (2006) · Annual Review of Genetics · doi:10.1146/annurev.genet.39.110304.095755 · Cited by 122
T-cell receptor ligation induces distinct signaling pathways in naïve vs. antigen-experienced T cells
Adachi, K., & Davis, M. M. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1017340108 · Cited by 111
Mitochondria Positioning Controls Local Calcium Influx in T Cells
Schwindling, C., Quintana, A., Krause, E., & Hoth, M. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0902872 · Cited by 110
Telomeres and immunological diseases of aging.
Andrews, N. P., Fujii, H., Goronzy, J. J., & Weyand, C. M. (2010) · Gerontology · doi:10.1159/000268620 · Cited by 108
Self-citation
Microclusters of inhibitory killer immunoglobulin–like receptor signaling at natural killer cell immunological synapses
Treanor, B., Lanigan, P. M. P., Kumar, S., Dunsby, C. W., Munro, I., Auksorius, E., Culley, F. J., Purbhoo, M. A., Phillips, D., Neil, M. A. A., et al. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200601108 · Cited by 107
CD94/NKG2A Inhibits NK Cell Activation by Disrupting the Actin Network at the Immunological Synapse
Masilamani, M., Nguyen, C. M.-C., Kabát, J., Borrego, F., & Coligan, J. E. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.6.3590 · Cited by 106
Formation of the Killer Ig-Like Receptor Repertoire on CD4+CD28null T Cells
Snyder, M. R., Muegge, L., Offord, C. P., O’Fallon, W. M., Bajzer, Ž., Weyand, C. M., & Goronzy, J. J. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.8.3839 · Cited by 104
Self-citation
Cytokine receptor signalling and aging
Fülöp, T., Larbi, A., Douziech, N., Levesque, I., Varin, A., & Herbein, G. (2006) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.01.025 · Cited by 104
Signal inhibition by the dual-specific phosphatase 4 impairs T cell-dependent B-cell responses with age
Yu, M., Li, G., Lee, W.-W., Yuan, M., Cui, D., Weyand, C. M., & Goronzy, J. J. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1109797109 · Cited by 102
Self-citation
The regulation of lymphocyte activation by inhibitory receptors
Leibson, P. J. (2004) · Current Opinion in Immunology · doi:10.1016/j.coi.2004.03.006 · Cited by 100
Signaling in thymic selection
Gascoigne, N. R. J., & Palmer, E. (2011) · Current Opinion in Immunology · doi:10.1016/j.coi.2010.12.017 · Cited by 98
Effect of Redox Balance Alterations on Cellular Localization of LAT and Downstream T-Cell Receptor Signaling Pathways
Gringhuis, S. I., der Voort, E. A. M. P.-V., Leow, A., Levarht, E. W. N., Breedveld, F. C., & Verweij, C. L. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.2.400-411.2002 · Cited by 93
Cutting Edge: Differential Segregation of the Src Homology 2-Containing Protein Tyrosine Phosphatase-1 Within the Early NK Cell Immune Synapse Distinguishes Noncytolytic from Cytolytic Interactions
Vyas, Y. M., Maniar, H. S., & Dupont, B. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.7.3150 · Cited by 86
Gene expression characteristics of CD28null memory phenotype CD8+ T cells and its implication in T‐cell aging
Fann, M., Chiu, W. K., Wood, W. H., Levine, B. L., Becker, K. G., & Weng, N. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00262.x · Cited by 83
Inhibition of Gluconeogenesis through Transcriptional Activation of EGR1 and DUSP4 by AMP-activated Kinase
Berasi, S. P., Huard, C., Li, D., Shih, H. H., Sun, Y. H., Zhong, W., Paulsen, J. E., Brown, E. L., Gimeno, R. E., & Martinez, R. V. P. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602416200 · Cited by 83
DNA-PKcs Controls an Endosomal Signaling Pathway for a Proinflammatory Response by Natural Killer Cells
Rajagopalan, S., Moyle, M. W., Joosten, I., & Long, E. O. (2010) · Science Signaling · doi:10.1126/scisignal.2000467 · Cited by 80
Mechanisms of immunosenescence: lessons from models of accelerated immune aging
Saux, S. L., Weyand, C. M., & Goronzy, J. J. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2011.06297.x · Cited by 76
Self-citation
Age-related differences in phenotype and function of CD4+ T cells are due to a phenotypic shift from naive to memory effector CD4+ T cells
Kovaiou, R. D., Weiskirchner, I., Keller, M., Pfister, G., Cioca, D., & Grubeck‐Loebenstein, B. (2005) · International Immunology · doi:10.1093/intimm/dxh314 · Cited by 76
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Authors: Goronzy, J. J., Li, G., Yu, M., & Weyand, C. M.
Affiliations: VA Palo Alto Health Care System (US)
Corresponding author: Goronzy, Jörg J.
ORCID: Goronzy, Jörg J.
Yu, Mingcan
Weyand, Cornelia M.
Venue: Seminars in Immunology
Publisher: Elsevier BV
Published: 2012-10
Volume: 24
Issue: 5
Pages: 365-372
ISSN: 1044-5323 (ISSN-L)
DOI: 10.1016/j.smim.2012.04.003
PMC: PMC3435478
OpenAlex: W2028580603
Cited by: 134
References: 123
Citations by year: 2026: 5 · 2025: 4 · 2024: 8 · 2023: 10 · 2022: 8 · 2021: 14 · 2020: 12 · 2019: 13 · 2018: 6 · 2017: 7 · 2016: 11 · 2015: 11 · 2014: 9 · 2013: 13 · 2012: 3
FWCI: 1.06
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Seminars in Immunology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Heart, Lung, and Blood Institute (P01HL058000, R01HL117913)
National Eye Institute (R01EY011916, R01 EY 11916)
National Institute of Allergy and Infectious Diseases (R01AI044142, U19-AI57266, R01AI44142, U19AI090019, U19AI057266)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR042527, R01AR42527)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: T cell senescence, signaling pathways, T cell differentiation, T cell homeostasis, CD8+ T cells, CD4+ T cells, CD28, TNF receptor superfamily, immunosenescence, autoimmunity, chronic infection, thymic function
MeSH terms: Aging, Animals, Cell Differentiation, Humans, Receptors, Antigen, T-Cell, T-Lymphocytes, Signal Transduction, Cellular Senescence

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Signaling pathways in aged T cells – A reflection of T cell differentiation, cell senescence and host environment

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