Dramatic increase in naïve T cell turnover is linked to loss of naïve T cells from old primates
Open accessAbstract
The loss of naïve T cells is a hallmark of immune aging. Although thymic involution is a primary driver of this naïve T cell loss, less is known about the contribution of other mechanisms to the depletion of naïve T cells in aging primates. We examined the role of homeostatic cycling and proliferative expansion in different T cell subsets of aging rhesus macaques (RM). BrdU incorporation and the expression of the G 1 -M marker Ki-67 were elevated in peripheral naïve CD4 and even more markedly in the naïve CD8 T cells of old, but not young adult, RM. Proliferating naïve cells did not accumulate in old animals. Rather, the relative size of the naïve CD8 T cell compartment correlated inversely to its proliferation rate. Likewise, T cell receptor diversity decreased in individuals with elevated naïve CD8 T cell proliferation. This apparent contradiction was explained by a significant increase in turnover concomitant with the naïve pool loss. The turnover increased exponentially when the naïve CD8 T cell pool decreased below 4% of total blood CD8 cells. These results link the shrinking naïve T cell pool with a dramatic increase in homeostatic turnover, which has the potential to exacerbate the progressive exhaustion of the naïve pool and constrict the T cell repertoire. Thus, homeostatic T cell proliferation exhibits temporal antagonistic pleiotropy, being beneficial to T cell maintenance in adulthood but detrimental to the long-term T cell maintenance in aging individuals.
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In later life, naive CD8+ T cells accelerate turnover.
“Only in later life, naive CD8+ T cells accelerate their turnover”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Cicin-Sain et al., 2007
Daily turnover of naive CD4+ and CD8+ T cells remains stable at about 0.04% throughout adulthood, with no apparent compensatory increase in homeostatic proliferation with age.
“Daily turnover rates of naive CD4+ and CD8+ T cells are stable throughout adulthood at about 0.04%, with no apparent need for compensatory increase in homeostatic proliferation with age.”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Cicin-Sain et al., 2007
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Pleiotropy, natural selection, and the evolution of senescence.
Williams, G. C. (1957) · Evolution · doi:10.1111/j.1558-5646.1957.tb02911.x · Cited by 4,279 · see citing works
Gerdes, J., Lemke, H., Baisch, H., Wacker, H. H., Schwab, U., & Stein, H. (1984) · The Journal of Immunology · doi:10.4049/jimmunol.133.4.1710 · Cited by 4,173 · see citing works
Age-related changes in lymphocyte development and function
Linton, P. J., & Dorshkind, K. A. (2004) · Nature Immunology · doi:10.1038/ni1033 · Cited by 1,180 · see citing works
The aging immune system: primer and prospectus
Miller, R. A. (1996) · Science · doi:10.1126/science.273.5271.70 · Cited by 1,165 · see citing works
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 · see citing works
Posnett, D. N., Sinha, R., Kabak, S., & Russo, C. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.179.2.609 · Cited by 761 · see citing works
Pannetier, C., Cochet, M., Darche, S., Casrouge, A., Zöller, M., & Kourilsky, P. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.9.4319 · Cited by 635 · see citing works
Cytokine Requirements for Acute and Basal Homeostatic Proliferation of Naive and Memory CD8+ T Cells
Goldrath, A. W., Sivakumar, P. V., Glaccum, M. B., Kennedy, M. K., Bevan, M. J., Benoist, C. O., Mathis, D. J., & Butz, E. A. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20020033 · Cited by 588 · see citing works
The many faces of IL-7: from lymphopoiesis to peripheral T cell maintenance
Fry, T. J., & Mackall, C. L. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.11.6571 · Cited by 563 · see citing works
T-cell repertoire diversity and clonal expansions in normal and clinical samples
Pannetier, C., Even, J., & Kourilsky, P. (1995) · Immunology Today · doi:10.1016/0167-5699(95)80117-0 · Cited by 551 · see citing works
Hadrup, S. R., Strindhall, J., Køllgaard, T., Seremet, T., Johansson, B. E. A., Pawelec, G., Straten, P. T., & Wikby, A. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.4.2645 · Cited by 471 · see citing works
Development and Homeostasis of T Cell Memory in Rhesus Macaque
Pitcher, C. J., Hagen, S. I., Walker, J. M., Lum, R., Mitchell, B. L., Maino, V. C., Axthelm, M. K., & Picker, L. J. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.1.29 · Cited by 467 · see citing works
Self-citationKimmig, S., Przybylski, G. K., Schmidt, C. A., Laurisch, K., Möwes, B., Radbruch, A., & Thiel, A. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20011756 · Cited by 439 · see citing works
Wikby, A., Ferguson, F., Forsey, R., Thompson, J., Strindhall, J., Löfgren, S., Nilsson, B.-O., Ernerudh, J., Pawelec, G., & Johansson, B. (2005) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/60.5.556 · Cited by 407 · see citing works
Wikby, A., Maxson, P., Olsson, J., Johansson, B. E. A., & Ferguson, F. G. (1998) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(97)00151-6 · Cited by 377 · see citing works
Clonal predominance of T cell receptors within the CD8+ CD45RO+ subset in normal human subjects.
Hingorani, R., Choi, I., Akolkar, P. N., Gulwani-Akolkar, B., Pergolizzi, R. G., Silver, J., & Gregersen, P. K. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.10.5762 · Cited by 282 · see citing works
Messaoudi, I., LeMaoult, J., Guevara-Patino, J. A., Metzner, B. M., & Nikolich‐Žugich, J. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20040437 · Cited by 243 · see citing works
Self-citationUnexpected expansions of CD8-bearing cells in old mice.
Callahan, J. E., Kappler, J. W., & Marrack, P. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.12.6657 · Cited by 228 · see citing works
Delay of T cell senescence by caloric restriction in aged long-lived nonhuman primates
Messaoudi, I., Warner, J., Fischer, M. B., Park, B., Hill, B. J., Mattison, J. A., Lane, M. A., Roth, G. S., Ingram, D. K., Picker, L. J., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0606661103 · Cited by 225 · see citing works
Self-citationVallejo, A. N., Brandes, J. C., Weyand, C. M., & Goronzy, J. J. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.11.6572 · Cited by 209 · see citing works
Evolutionary Theories of Aging and Longevity
Gavrilov, L. A., & Gavrilova, N. S. (2002) · The Scientific World JOURNAL · doi:10.1100/tsw.2002.96 · Cited by 201 · see citing works
Dysfunctional CMV-specific CD8+ T cells accumulate in the elderly
Ouyang, Q., Wagner, W. M., Zheng, W., Wikby, A., Remarque, E. J., & Pawelec, G. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2003.11.016 · Cited by 179 · see citing works
Garcia, G. G., & Miller, R. A. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.5.3151 · Cited by 123 · see citing works
Nikolich‐Žugich, J., & Messaoudi, I. (2005) · Experimental Gerontology · doi:10.1016/j.exger.2005.06.007 · Cited by 112 · see citing works
Self-citationSeggewiss, R., Loré, K., Guenaga, J., Pittaluga, S., Mattapallil, J. J., Chow, C. K., Koup, R. A., Camphausen, K. A., Nason, M., Meier‐Schellersheim, M., et al. (2007) · Blood · doi:10.1182/blood-2006-12-065623 · Cited by 99 · see citing works
Age-Related Dysregulation in CD8 T Cell Homeostasis: Kinetics of a Diversity Loss
LeMaoult, J., Messaoudi, I., Manavalan, J. S., Potvin, H., Nikolich-Žugich, D., Dyall, R., Szabo, P., Weksler, M. E., & Nikolich‐Žugich, J. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.5.2367 · Cited by 96 · see citing works
Self-citationRibeiro, R. M., Hazenberg, M. D., Perelson, A. S., & Davenport, M. P. (2005) · Journal of Virology · doi:10.1128/jvi.80.2.802-809.2006 · Cited by 84 · see citing works
Regulation of naïve and memory T-cell homeostasis
Surh, C. D., & Sprent, J. (2002) · Microbes and Infection · doi:10.1016/s1286-4579(01)01509-x · Cited by 77 · see citing works
Janković, V., Messaoudi, I., & Nikolich‐Žugich, J. (2003) · Blood · doi:10.1182/blood-2003-03-0927 · Cited by 75 · see citing works
Self-citationMoniuszko, M., Fry, T., Tsai, W.-P., Morre, M., Assouline, B., Cortez, P., Lewis, M. G., Cairns, S., Mackall, C., & Franchini, G. (2004) · Journal of Virology · doi:10.1128/jvi.78.18.9740-9749.2004 · Cited by 74 · see citing works
Current concepts of thymic aging
Fry, T. J., & Mackall, C. L. (2002) · Springer Seminars in Immunopathology · doi:10.1007/s00281-001-0092-5 · Cited by 62 · see citing works
From Hayflick to Walford: the role of T cell replicative senescence in human aging
Effros, R. B. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2004.03.004 · Cited by 61 · see citing works
Messaoudi, I., Warner, J., Nikolich-Žugich, D., Fischer, M. B., & Nikolich‐Žugich, J. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.1.301 · Cited by 53 · see citing works
Self-citationConserved T-cell receptor repertoire in simian immunodeficiency virus-infected rhesus monkeys.
Chen, Z. W., Kou, Z. C., Shen, L., Reimann, K. A., & Letvin, N. L. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.4.2177 · Cited by 51 · see citing works
Between Scylla and Charybdis: p53 links tumor suppression and aging
Campisi, J. (2002) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(02)00006-4 · Cited by 33 · see citing works
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Goronzy, J. J., & Weyand, C. M. (2013) · Nature Immunology · doi:10.1038/ni.2588 · Cited by 827 · see citing works
Diversity and clonal selection in the human T-cell repertoire
Qi, Q., Liu, Y., Cheng, Y., Glanville, J., Zhang, D., Lee, J.-Y., Olshen, R. A., Weyand, C. M., Boyd, S. D., & Goronzy, J. J. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1409155111 · Cited by 755 · see citing works
Immunosenescence and human vaccine immune responses
Crooke, S. N., Ovsyannikova, I. G., Poland, G. A., & Kennedy, R. B. (2019) · Immunity & Ageing · doi:10.1186/s12979-019-0164-9 · Cited by 530 · see citing works
The Effect of Age on Thymic Function
Palmer, D. B. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00316 · Cited by 494 · see citing works
Britanova, O. V., Putintseva, E. V., Shugay, M., Merzlyak, E. M., Turchaninova, M. A., Staroverov, D. B., Bolotin, D. A., Lukyanov, S., Bogdanova, E. A., Mamedov, I. Z., et al. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1302064 · Cited by 465 · see citing works
Ageing and life-long maintenance of T-cell subsets in the face of latent persistent infections.
Nikolich-Žugich, J. (2008) · Nature reviews. Immunology · doi:10.1038/nri2318 · Cited by 463 · see citing works
Self-citationSuccessful and Maladaptive T Cell Aging
Goronzy, J. J., & Weyand, C. M. (2017) · Immunity · doi:10.1016/j.immuni.2017.03.010 · Cited by 362 · see citing works
Wertheimer, A. M., Bennett, M. S., Park, B., Uhrlaub, J. L., Martinez, C., Pulko, V., Currier, N. L., Nikolich-Žugich, D., Kaye, J., & Nikolich-Žugich, J. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1301721 · Cited by 352 · see citing works
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Aging of the T Cell Compartment in Mice and Humans: From No Naive Expectations to Foggy Memories
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van den Broek, T., Borghans, J. A. M., & van Wijk, F. (2018) · Nature reviews. Immunology · doi:10.1038/s41577-018-0001-y · Cited by 258 · see citing works
Premature aging of circulating T cells in patients with end-stage renal disease
Betjes, M. G. H., Langerak, A. W., van der Spek, A., de Wit, E. A., & Litjens, N. H. R. (2011) · Kidney International · doi:10.1038/ki.2011.110 · Cited by 207 · see citing works
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Pulko, V., Davies, J. S., Martinez, C., Lanteri, M. C., Busch, M. P., Diamond, M. S., Knox, K., Bush, E. C., Sims, P. A., Sinari, S., et al. (2016) · Nature Immunology · doi:10.1038/ni.3483 · Cited by 175 · see citing works
Self-citationTsukamoto, H., Clise-Dwyer, K., Huston, G. E., Duso, D. K., Buck, A. L., Johnson, L. L., Haynes, L., & Swain, S. L. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910139106 · Cited by 166 · see citing works
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Zhang, H., Weyand, C. M., & Goronzy, J. J. (2021) · FEBS Journal · doi:10.1111/febs.15770 · Cited by 177 · see citing works
Gain and loss of T cell subsets in old age: age-related reshaping of the T cell repertoire.
Arnold, C. R., Wolf, J., Brunner, S., Herndler-Brandstetter, D., & Grubeck-Loebenstein, B. (2011) · Journal of Clinical Immunology · doi:10.1007/s10875-010-9499-x · Cited by 170 · see citing works
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Messaoudi, I., Estep, R. D., Robinson, B. A., & Wong, S. W. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3241 · Cited by 166 · see citing works
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Self-citationČičin‐Šain, L., Smyk-Pearson, S., Currier, N., Byrd, L., Koudelka, C. W., Robinson, T., Swarbrick, G. M., Tackitt, S., Legasse, A. W., Fischer, M. B., et al. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0904193 · Cited by 147 · see citing works
Self-citationLake, M. A., Ambrose, L. R., Lipman, M. C. I., & Lowe, D. M. (2016) · BMC Medicine · doi:10.1186/s12916-016-0606-6 · Cited by 136 · see citing works
Goronzy, J. J., Li, G., Yu, M., & Weyand, C. M. (2012) · Seminars in Immunology · doi:10.1016/j.smim.2012.04.003 · Cited by 134 · see citing works
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Boehm, T. L. J., Hirano, M., Holland, S. J., Das, S., Schorpp, M., & Cooper, M. D. (2017) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042617-053028 · Cited by 132 · see citing works
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Ardia, D. R., Parmentier, H. K., & Vogel, L. A. (2010) · Functional Ecology · doi:10.1111/j.1365-2435.2010.01759.x · Cited by 130 · see citing works
Lutz, C. T., Karapetyan, A., Al-Attar, A., Shelton, B. J., Holt, K. J., Tucker, J. H., & Presnell, S. R. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1002732 · Cited by 118 · see citing works
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Ahmed, M., Lanzer, K. G., Yager, E. J., Adams, P. S., Johnson, L. L., & Blackman, M. A. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.182.2.784 · Cited by 123 · see citing works
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Appay, V., & Sauce, D. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.01.003 · Cited by 118 · see citing works
Expression of p16INK4a prevents cancer and promotes aging in lymphocytes
Liu, Y., Johnson, S. M., Fedoriw, Y., Rogers, A. B., Yuan, H., Krishnamurthy, J., & Sharpless, N. E. (2011) · Blood · doi:10.1182/blood-2010-09-304402 · Cited by 114 · see citing works
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Mitchell, W. A., Lang, P.-O., & Aspinall, R. (2010) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2010.04209.x · Cited by 114 · see citing works
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Ferrando‐Martínez, S., Ruíz-Mateos, E., Hernández, A., Gutiérrez, E., Rodríguez-Méndez, M. M., Ordóñez, A., & Leal, M. (2010) · AGE · doi:10.1007/s11357-010-9170-8 · Cited by 109 · see citing works
Renkema, K. R., Li, G., Wu, A., Smithey, M. J., & Nikolich‐Žugich, J. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1301453 · Cited by 109 · see citing works
Self-citationLymphocyte maintenance during healthy aging requires no substantial alterations in cellular turnover
Westera, L., van Hoeven, V., Drylewicz, J., Spierenburg, G., van Velzen, J. F., de Boer, R. J., Tesselaar, K., & Borghans, J. A. M. (2015) · Aging Cell · doi:10.1111/acel.12311 · Cited by 96 · see citing works
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Johnson, P. L. F., Yates, A. J., Goronzy, J. J., & Antia, R. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1209283110 · Cited by 94 · see citing works
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Gil, A., Yassai, M. B., Naumov, Y. N., & Selin, L. K. (2015) · Journal of Virology · doi:10.1128/jvi.03020-14 · Cited by 78 · see citing works
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Tsukamoto, H., Huston, G. E., Dibble, J. P., Duso, D. K., & Swain, S. L. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1001668 · Cited by 57 · see citing works
Aging and Options to Halt Declining Immunity to Virus Infections
Palacios-Pedrero, M. Á., Osterhaus, A. D. M. E., Becker, T., Elbahesh, H., Rimmelzwaan, G. F., & Saletti, G. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.681449 · Cited by 55 · see citing works
Contreras, N. A., Fontana, L., Tosti, V., & Nikolich‐Žugich, J. (2018) · GeroScience · doi:10.1007/s11357-018-0022-2 · Cited by 53 · see citing works
Self-citationLang, A. M., Brien, J. D., Messaoudi, I., & Nikolich‐Žugich, J. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.7.4848 · Cited by 45 · see citing works
Self-citationImmune senescence in aged nonhuman primates☆
Haberthur, K., Engelmann, F., Barron, A., & Messaoudi, I. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.06.001 · Cited by 44 · see citing works
Self-citationEffect of IL-7 Therapy on Naive and Memory T Cell Homeostasis in Aged Rhesus Macaques
Okoye, A. A., Rohankhedkar, M., Konfe, A. L., Abana, C. O., Reyes, M. D., Clock, J. A., Duell, D. M., Sylwester, A. W., Sammader, P., Legasse, A. W., et al. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500609 · Cited by 44 · see citing works
Self-citationUse it or lose it: establishment and persistence of T cell memory
Kedzierska, K., Valkenburg, S., Doherty, P., Davenport, M., & Venturi, V. (2012) · Front. Immun. · doi:10.3389/fimmu.2012.00357 · Cited by 43 · see citing works
Maintenance of naïve CD8 T cells in nonagenarians by leptin, IGFBP3 and T3
Chen, J., Li, J., Lim, F. C., Wu, Q., Douek, D. C., Scott, D. K., Ravussin, É., Hsu, H., Jazwinski, S. M., & Mountz, J. D. (2009) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2009.11.003 · Cited by 42 · see citing works
Hansen, S. G., Womack, J. L., Scholz, I., Renner, A., Edgel, K. A., Xu, G., Ford, J. C., Grey, M., Laurent, B. S., Turner, J. M., et al. (2019) · PLoS ONE · doi:10.1371/journal.pone.0210252 · Cited by 41 · see citing works
Self-citationThe interplay between immune maturation, age, chronic viral infection and environment
Oxford, K. L., Pena-Ponce, M. G. D., Jensen, K., Eberhardt, M. K., Spinner, A., Rompay, K. K. A. V., Rigdon, J., Mollan, K. R., Krishnan, V., Hudgens, M. G., et al. (2015) · Immunity & Ageing · doi:10.1186/s12979-015-0030-3 · Cited by 37 · see citing works
On the Role of CD8+ T Cells in Determining Recovery Time from Influenza Virus Infection
Cao, P., Wang, Z., Yan, A. W. C., McVernon, J., Xu, J., Heffernan, J. M., Kedzierska, K., & McCaw, J. M. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00611 · Cited by 37 · see citing works
Age-associated parallel increase of Foxp3+CD4+ regulatory and CD44+CD4+ memory T cells in SJL/J mice
Han, G.-M., Zhao, B., Jeyaseelan, S., & Feng, J.-M. (2009) · Cellular Immunology · doi:10.1016/j.cellimm.2009.05.003 · Cited by 35 · see citing works
Mirza, N. N., Pollock, K., Hoelzinger, D. B., Dominguez, A. L., & Lustgarten, J. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2011.00730.x · Cited by 33 · see citing works
Johnson, P. L. F., Goronzy, J. J., & Antia, R. (2014) · Immunology · doi:10.1111/imm.12244 · Cited by 34 · see citing works
Intrinsic and extrinsic contributors to defective CD8+ T cell responses with aging
Jergović, M., Smithey, M. J., & Nikolich‐Žugich, J. (2018) · Experimental Gerontology · doi:10.1016/j.exger.2018.01.011 · Cited by 33 · see citing works
Self-citationAge-related differences in immune dynamics during SARS-CoV-2 infection in rhesus macaques
Speranza, E. E., Purushotham, J. N., Port, J. R., Schwarz, B. H., Flagg, M., Williamson, B. N., Feldmann, F., Singh, M., Pérez-Pérez, L., Sturdevant, G. L., et al. (2022) · Life Science Alliance · doi:10.26508/lsa.202101314 · Cited by 29 · see citing works
Impact of ageing on the response and repertoire of influenza virus-specific CD4 T cells
Lanzer, K. G., Johnson, L. L., Woodland, D. L., & Blackman, M. A. (2014) · Immunity & Ageing · doi:10.1186/1742-4933-11-9 · Cited by 30 · see citing works
Cellular senescence is a key mediator of lung aging and susceptibility to infection
Torrance, B. L., & Haynes, L. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1006710 · Cited by 28 · see citing works
T Cell Subsets in the Germinal Center: Lessons from the Macaque Model
Vaccari, M., & Franchini, G. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00348 · Cited by 29 · see citing works
Premature aging of circulating T cells predicts all-cause mortality in hemodialysis patients
Xiang, F., Chen, R., Cao, X., Shen, B., Chen, X., Ding, X., & Zou, J. (2020) · BMC Nephrology · doi:10.1186/s12882-020-01920-8 · Cited by 29 · see citing works
Sharma, R., Diwan, B., Sharma, A., & Witkowski, J. M. (2022) · Biogerontology · doi:10.1007/s10522-022-09995-6 · Cited by 29 · see citing works
Zheng, H., Zhang, M., Pang, W., & Zheng, Y. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.04.004 · Cited by 27 · see citing works
Cytomegalovirus and immune senescence: Culprit or innocent bystander?
Karrer, U. W., Mekker, A., Wanke, K., Tchang, V. S., & Haeberli, L. (2009) · Experimental Gerontology · doi:10.1016/j.exger.2009.09.003 · Cited by 24 · see citing works
Immune Response to the West Nile Virus in Aged Non-Human Primates
Wertheimer, A. M., Uhrlaub, J. L., Hirsch, A. J., Medigeshi, G. R., Sprague, J., Legasse, A. W., Wilk, J., Wiley, C. A., Didier, P. J., Tesh, R. B., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015514 · Cited by 23 · see citing works
Self-citationDAMPs and influenza virus infection in ageing
Samy, R. P., & Lim, L. H. K. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.07.005 · Cited by 22 · see citing works
Extraction and characterization of the rhesus macaque T‐cell receptor β‐chain genes
Greenaway, H. Y., Kurniawan, M., Price, D. A., Douek, D. C., Davenport, M. P., & Venturi, V. (2009) · Immunology and Cell Biology · doi:10.1038/icb.2009.38 · Cited by 22 · see citing works
Štrbo, N., Vaccari, M., Pahwa, S. G., Kolber, M. A., Fisher, E., Gonzalez, L. E., Doster, M. N., Hryniewicz, A., Felber, B. K., Pavlakis, G. N., et al. (2011) · Vaccine · doi:10.1016/j.vaccine.2011.01.044 · Cited by 21 · see citing works
Hart, B. A. ‘., Jagessar, S. A., Kap, Y. S., Haanstra, K. G., Philippens, I. H. C. H. M., Serguera, C., Langermans, J. A. M., & Vierboom, M. (2014) · Drug Discovery Today · doi:10.1016/j.drudis.2014.03.023 · Cited by 20 · see citing works
Non-human primate models of T-cell reconstitution
Nikolich‐Žugich, J. (2007) · Seminars in Immunology · doi:10.1016/j.smim.2007.10.003 · Cited by 20 · see citing works
Self-citationBetter safe than sorry: Naive T-cell dynamics in healthy ageing
de Boer, R. J., Tesselaar, K., & Borghans, J. A. M. (2023) · Seminars in Immunology · doi:10.1016/j.smim.2023.101839 · Cited by 19 · see citing works
Valkenburg, S. A., Venturi, V., Dang, T. H. Y., Bird, N. L., Doherty, P. C., Turner, S. J., Davenport, M. P., & Kedzierska, K. (2012) · PLoS Pathogens · doi:10.1371/annotation/e142f9de-7f30-4759-bda1-a651e86d5ba6 · Cited by 19 · see citing works
Shaping the T‐cell repertoire in the periphery
Allen, S. M., Turner, S. J., Bourges, D., Gleeson, P. A., & van Driel, I. R. (2010) · Immunology and Cell Biology · doi:10.1038/icb.2010.133 · Cited by 17 · see citing works
Zheng, H., Zhang, M., Chen, M., Jiang, J., Song, J.-H., Lian, X., Tian, R., Zhang, X.-L., Zhang, L., Pang, W., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-00084-0 · Cited by 17 · see citing works
Memory T Cells in Rhesus Macaques
Vaccari, M., & Franchini, G. (2010) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-6451-9_10 · Cited by 17 · see citing works
Adaptive Immunity and Metabolic Health: Harmony Becomes Dissonant in Obesity and Aging
Bharath, L. P., Ip, B. C., & Nikolajczyk, B. S. (2017) · Comprehensive physiology · doi:10.1002/cphy.c160042 · Cited by 17 · see citing works
Immunosenescence and Inflammaging in COVID-19
Asghari, F., Asghary, A., Zolbanin, N. M., Faraji, F., & Jafari, R. (2023) · Viral Immunology · doi:10.1089/vim.2023.0045 · Cited by 16 · see citing works
Workshop on Immunizations in Older Adults: Identifying Future Research Agendas
High, K. P., D’Aquila, R. T., Fuldner, R., Gerding, D. N., Halter, J. B., Haynes, L., Hazzard, W. R., Jackson, L. A., Janoff, E. N., Levin, M. J., et al. (2010) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2010.02772.x · Cited by 15 · see citing works
Uremia-Associated Immunological Aging and Severity of COVID-19 Infection
Betjes, M. G. H. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.675573 · Cited by 14 · see citing works
Improving immunity in the elderly: current and future lessons from nonhuman primate models
Meyer, C., Kerns, A. R., Haberthur, K., & Messaoudi, I. (2011) · AGE · doi:10.1007/s11357-011-9353-y · Cited by 14 · see citing works
Self-citationSingle‐cell transcriptomic analysis of the senescent microenvironment in bone metastasis
Wang, S., Ao, L., Lin, H., Wei, H., Wu, Z., Lu, S., Liang, F., Shen, R., Zhang, H., Miao, T., et al. (2024) · Cell Proliferation · doi:10.1111/cpr.13743 · Cited by 13 · see citing works
Zhang, Y., de Lara, C., Worth, A. T., Hegedus, A., Laamanen, K., Beverley, P. C. L., & Macallan, D. C. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003310 · Cited by 13 · see citing works
The Hayflick Limit May Determine the Effective Clonal Diversity of Naive T Cells
Ndifon, W. O., & Dushoff, J. G. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1502343 · Cited by 11 · see citing works
Aging of the Immune System Across Different Species
Nikolich-Žugich, J., & Čičin-Šain, L. (2010) · The Comparative Biology of Aging · doi:10.1007/978-90-481-3465-6_15 · Cited by 9 · see citing works
Self-citationUhrlaub, J. L., Jergović, M., Bradshaw, C. M., Sonar, S. A., Coplen, C. P., Dudakov, J. A., Murray, K. O., Lanteri, M. C., Busch, M. P., van den Brink, M. R. M., et al. (2022) · Aging Cell · doi:10.1111/acel.13582 · Cited by 7 · see citing works
Self-citationWatanabe, M., Maruo, T., & Suzuki, T. (2023) · International Journal of Food Sciences and Nutrition · doi:10.1080/09637486.2023.2236805 · Cited by 5 · see citing works
Lanzer, K. G., Cookenham, T. S., Lehrmann, E., Zhang, Y., Duso, D., Xie, Q., Reiley, W. W., Becker, K. G., & Blackman, M. A. (2023) · ImmunoHorizons · doi:10.4049/immunohorizons.2200066 · Cited by 5 · see citing works
Age-associated T-cell Clonal Expansions (TCE) in vivo—Implications for Pathogen Resistance
Nikolich‐Žugich, J., & Lang, A. M. (2009) · Springer eBooks · doi:10.1007/978-1-4020-9063-9_12 · Cited by 4 · see citing works
Self-citationAdaptive Immunity and Metabolic Health: Harmony Becomes Dissonant in Obesity and Aging
Bharath, L. P., Ip, B. C., & Nikolajczyk, B. S. (2017) · Comprehensive physiology · doi:10.1002/j.2040-4603.2017.tb00780.x · Cited by 4 · see citing works
Age, T-cell Homeostasis, and T-cell Diversity in Humans
Lamar, D. L., Weyand, C. M., & Goronzy, J. J. (2009) · Springer eBooks · doi:10.1007/978-1-4020-9063-9_9 · Cited by 4 · see citing works
- Authors
- Čičin-Šain, L., Messaoudi, I., Park, B., Currier, N., Planer, S., Fischer, M., Tackitt, S., Nikolich-Žugich, D., Legasse, A., Axthelm, M. K., Picker, L. J., Mori, M., & Nikolich-Žugich, J.
- Affiliations
- *Vaccine and Gene Therapy Institute and
- Oregon Health & Science University (US)
- Oregon National Primate Research Center (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-12-11
- Volume
- 104
- Issue
- 50
- Pages
- 19960-19965
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2148405
- OpenAlex
- W1995716646
- Cited by
- 129
- References
- 35
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 5 · 2022: 5 · 2021: 8 · 2020: 2 · 2019: 8 · 2018: 6 · 2017: 9 · 2016: 8 · 2015: 6 · 2014: 12 · 2013: 11 · 2012: 9
- FWCI
- 3.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- U.S. Public Health Service
- Oregon National Primate Research Center
- National Institute on Aging (P01AG023664, U01AG021384)
- National Center for Research Resources (RR-0163, P51RR000163, K01RR000163)
- 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 › Virology › HIV Research and Treatment
- Keywords
- immunosenescence, naive T cells, T cell turnover, homeostatic proliferation, naive CD8+ T cells, naive CD4+ T cells, T cell receptor diversity, rhesus monkeys, Ki-67, antagonistic pleiotropy, thymic involution, T cell exhaustion
- MeSH terms
- Aging, Animals, Female, Homeostasis, Immunity, Innate, Immunologic Memory, Kinetics, Macaca mulatta, Male, T-Lymphocytes, Ki-67 Antigen, Cell Proliferation
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