Cited by 466T-cell and B-cell ImmunologyTelomeres, Telomerase, and SenescenceHIV Research and Treatment

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Ageing and life-long maintenance of T-cell subsets in the face of latent persistent infections.

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Nikolich-Žugich, Janko·2008·Nature reviews. Immunology

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Abstract

A diverse and well-balanced repertoire of T cells is thought to be crucial for the efficacious defence against infection with new or re-emerging pathogens throughout life. In the last third of the mammalian lifespan, the maintenance of a balanced T-cell repertoire becomes highly challenging because of the changes in T-cell production and consumption. In this Review, I question whether latent persistent pathogens might be key factors that drive this imbalance and whether they determine the extent of age-associated immune deficiency.

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Two subsets of memory T lymphocytes with distinct homing potentials and effector functions
Sallusto, F., Lenig, D., Förster, R., Lipp, M., & Lanzavecchia, A. (1999) · Nature · doi:10.1038/44385 · Cited by 5,846 · cited 1×
“Following encounter with antigen, naive T cells first generate effector T cells (CD69 hi CD25 hi CCR7 low CD62L low CD127 low CD27 low ) and then memory T cells, which can be broadly divided into central memory T cells (CD69 − CD25 − CCR7 hi CD62L hi CD127 hi CD27 hi ) and effector memory T cells (CD69 − CD25 − CCR7 h…”
Background
PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression
Day, C. L., Kaufmann, D. E., Kiepiela, P., Brown, J. A., Moodley, E. S., Reddy, S., Mackey, E. W., Miller, J. D., Leslie, A. J., DePierres, C., et al. (2006) · Nature · doi:10.1038/nature05115 · Cited by 2,680
Broadly targeted human cytomegalovirus-specific CD4 + and CD8 + T cells dominate the memory compartments of exposed subjects
Sylwester, A. W., Mitchell, B. L., Edgar, J. B., Taormina, C., Pelte, C., Ruchti, F., Sleath, P. R., Grabstein, K. H., Hosken, N. A., Kern, F., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050882 · Cited by 1,339
Age-related changes in lymphocyte development and function
Linton, P. J., & Dorshkind, K. A. (2004) · Nature Immunology · doi:10.1038/ni1033 · Cited by 1,199
The aging immune system: primer and prospectus
Miller, R. A. (1996) · Science · doi:10.1126/science.273.5271.70 · Cited by 1,165 · cited 1×
“jpg" NDATA ITEM> ]> Ageing of the immune system involves a complex set of changes that are collectively termed immune senescence (reviewed in Ref”
Background
Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells
Brenchley, J. M., Karandikar, N. J., Betts, M. R., Ambrozak, D. R., Hill, B. J., Crotty, L. E., Casazza, J. P., Kuruppu, J., Migueles, S. A., Connors, M., et al. (2003) · Blood · doi:10.1182/blood-2002-07-2103 · Cited by 1,073 · cited 1×
“, and CD57, which has been shown in HIV-infected subjects to mark replicatively senescent cells likely to undergo apoptosi”
Background
Interleukin-10 determines viral clearance or persistence in vivo
Brooks, D. G., Trifilo, M. J., Edelmann, K. H., Teyton, L., McGavern, D. B., & Oldstone, M. B. A. (2006) · Nature Medicine · doi:10.1038/nm1492 · Cited by 937 · cited 1×
“, as well as the blockade of IL-10, a cytokine often associated with inhibition of type 1 immunit”
Background
PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection
Petrovas, C., Casazza, J. P., Brenchley, J. M., Price, D. A., Gostick, E., Adams, W. C., Precopio, M. L., Schacker, T., Roederer, M., Douek, D. C., et al. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20061496 · Cited by 889
Differential Requirements for Survival and Proliferation of CD8 Naïve or Memory T Cells
Tanchot, C., Lemonnier, F. A., Pérarnau, B., Freitas, A. A., & Rocha, B. (1997) · Science · doi:10.1126/science.276.5321.2057 · Cited by 856
Fuel feeds function: energy metabolism and the T-cell response
Fox, C. J., Hammerman, P. S., & Thompson, C. B. (2005) · Nature reviews. Immunology · doi:10.1038/nri1710 · Cited by 841 · cited 1×
“Although we have precise information on the role of cytokines (primarily IL-7, IL-15 and IL-2) and self-peptide–MHC complexes, it is less clear how metabolic signal”
Background
Immunosenescence of ageing
Gruver, A., Hudson, L., & Sempowski, G. (2007) · The Journal of Pathology · doi:10.1002/path.2104 · Cited by 834
Tolerance, not immunity, crucially depends on IL-2
Malek, T. R., & Bayer, A. L. (2004) · Nature reviews. Immunology · doi:10.1038/nri1435 · Cited by 819 · cited 1×
“IL-2 has been shown to oppose some of the actions of IL-7 and IL-15 and its main homeostatic role is probably in the production and expansion of regulatory T cells”
Background
Control of Homeostasis of CD8 + Memory T Cells by Opposing Cytokines
Ku, C., Murakami, M., Sakamoto, A., Kappler, J. W., & Marrack, P. (2000) · Science · doi:10.1126/science.288.5466.675 · Cited by 814
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
Interleukin (IL)-15 and IL-7 Jointly Regulate Homeostatic Proliferation of Memory Phenotype CD8+ Cells but Are Not Required for Memory Phenotype CD4+ Cells
Tan, J. T., Ernst, B., Kieper, W. C., LeRoy, E., Sprent, J., & Surh, C. D. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20020066 · Cited by 790
Herpesvirus latency confers symbiotic protection from bacterial infection
Barton, E. S., White, D. W., Cathelyn, J. S., Brett-McClellan, K. A., Engle, M., Diamond, M. S., Miller, V. L., & Virgin, H. W. (2007) · Nature · doi:10.1038/nature05762 · Cited by 763
Clonal populations of T cells in normal elderly humans: the T cell equivalent to "benign monoclonal gammapathy".
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
Epidemiology of Invasive Streptococcus pneumoniae Infections in the United States, 1995-1998 Opportunities for Prevention in the Conjugate Vaccine Era
Robinson, K. A. (2001) · JAMA · doi:10.1001/jama.285.13.1729 · Cited by 654 · cited 1×
“Key immunological manifestations of immune senescence include poor responsiveness to new or evolving pathogens and reduced efficacy of vaccination-induced protection against infectio”
Background
Naive T Cells Transiently Acquire a Memory-like Phenotype during Homeostasis-Driven Proliferation
Goldrath, A. W., Bogatzki, L. Y., & Bevan, M. J. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.4.557 · Cited by 637
Lifespan of human lymphocyte subsets defined by CD45 isoforms
Michie, C. A., McLean, A. R., Alcock, C. J., & Beverley, P. C. L. (1992) · Nature · doi:10.1038/360264a0 · Cited by 635 · cited 1×
“Several published manuscripts have described an accumulation of dysfunctional or hypofunctional cells with a 'terminally differentiated' phenotype that is associated with human agein”
Background
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
Handbook of the Biology of Aging
(1986) · Journal of Gerontology · doi:10.1093/geronj/41.1.120 · Cited by 563
Thymus cell migration: Quantitative aspects of cellular traffic from the thymus to the periphery in mice
Scollay, R. G., Butcher, E. C., & Weissman, I. L. (1980) · European Journal of Immunology · doi:10.1002/eji.1830100310 · Cited by 555
Thymopoiesis independent of common lymphoid progenitors.
Allman, D., Sambandam, A., Kim, S., Miller, J. P., Pagan, A., Well, D., Meraz, A., & Bhandoola, A. (2003) · Nature Immunology · doi:10.1038/ni878 · Cited by 544 · cited 1×
“Most of the recent studies have implicated defects in the commitment of haematopoietic stem cells to the lymphoid lineage and the migration of these lymphoid-restricted precursors (known as early T-cell progenitor”
Background
Homeostasis-Stimulated Proliferation Drives Naive T Cells to Differentiate Directly into Memory T Cells
Cho, B. K., Rao, V. P., Ge, Q., Eisen, H. N., & Chen, J. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.4.549 · Cited by 509
Age-related change in peripheral blood T-lymphocyte subpopulations and cytomegalovirus infection in the very old: the Swedish longitudinal OCTO immune study
Olsson, J., Wikby, A., Johansson, B., Löfgren, S., Nilsson, B.-O., & Ferguson, F. G. (2001) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(00)00210-4 · Cited by 474
Longitudinal Studies of Clonally Expanded CD8 T Cells Reveal a Repertoire Shrinkage Predicting Mortality and an Increased Number of Dysfunctional Cytomegalovirus-Specific T Cells in the Very Elderly
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
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
Memory Inflation: Continuous Accumulation of Antiviral CD8+ T Cells Over Time
Karrer, U. W., Sierro, S. R., Wagner, M., Oxenius, A., Hengel, H., Koszinowski, U. H., Phillips, R. E., & Klenerman, P. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.4.2022 · Cited by 444
Population Biology of Lymphocytes: The Flight for Survival
Freitas, A. A., & Rocha, B. (2000) · Annual Review of Immunology · doi:10.1146/annurev.immunol.18.1.83 · Cited by 435
Genetics and the Specificity of the Aging Process
Hekimi, S., & Guarente, L. (2003) · Science · doi:10.1126/science.1082358 · Cited by 434 · cited 1×
“The primary alterations result from several partially overlapping processes that include, but are not limited to, DNA damage, oxidative stress (such as peroxidation of lipids, proteins and sugars) and reduced macromolecular biosynthesis, degradation and turnove”
Background
An Immune Risk Phenotype, Cognitive Impairment, and Survival in Very Late Life: Impact of Allostatic Load in Swedish Octogenarian and Nonagenarian Humans
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 · cited 1×
“, as well as with shorter lifespan in octogenarian”
Background
Long-Term Cytomegalovirus Infection Leads to Significant Changes in the Composition of the CD8+T-Cell Repertoire, Which May Be the Basis for an Imbalance in the Cytokine Production Profile in Elderly Persons
Almanzar, G., Schwaiger, S., Jenewein, B., Keller, M., Herndler‐Brandstetter, D., Würzner, R., Schönitzer, D., & Grubeck‐Loebenstein, B. (2005) · Journal of Virology · doi:10.1128/jvi.79.6.3675-3683.2005 · Cited by 356
Acquisition of direct antiviral effector functions by CMV-specific CD4+ T lymphocytes with cellular maturation
Casazza, J. P., Betts, M. R., Price, D. A., Precopio, M., Ruff, L. E., Brenchley, J. M., Hill, B. J., Roederer, M., Douek, D. C., & Koup, R. A. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20052246 · Cited by 338
Thymic output in aged mice
Hale, J. S., Boursalian, T. E., Turk, G. L., & Fink, P. J. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601040103 · Cited by 322 · cited 1×
“The rate of production of these recent thymic emigrants (RTEs) is proportional to the total thymic mass, and amounts to ∼1% of the total thymic cell content per da”
Background
Stimulation History Dictates Memory CD8 T Cell Phenotype: Implications for Prime-Boost Vaccination
Masopust, D., Ha, S., Vezys, V., & Ahmed, R. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.2.831 · Cited by 313
Ageing of lymphocytes and lymphocytes in the aged
Globerson, A., & Effros, R. B. (2000) · Immunology Today · doi:10.1016/s0167-5699(00)01714-x · Cited by 313
The Role of the Thymus and Recent Thymic Migrants in the Maintenance of the Adult Peripheral Lymphocyte Pool
Berzins, S. P., Boyd, R. L., & Miller, J. F. A. P. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.187.11.1839 · Cited by 291 · cited 1×
“The maintenance and survival of naive T cells is countered by the regular replacement of naive T cells by RTEs in a random manner to ensure diversity of the naive T-cell poo”
Background
The Effect of Aging on Susceptibility to Infection
Gardner, I. (1980) · Clinical Infectious Diseases · doi:10.1093/clinids/2.5.801 · Cited by 284
The immune risk phenotype is associated with IL-6 in the terminal decline stage: Findings from the Swedish NONA immune longitudinal study of very late life functioning
Wikby, A., Nilsson, B.-O., Forsey, R. J., Thompson, J., Strindhall, J., Löfgren, S., Ernerudh, J., Pawelec, G., Ferguson, F. G., & Johansson, B. E. A. (2006) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.04.003 · Cited by 284
Homeostasis of memory T cells
Surh, C. D., Boyman, O., Purton, J. F., & Sprent, J. (2006) · Immunological Reviews · doi:10.1111/j.0105-2896.2006.00401.x · Cited by 277
CD4 T cell memory derived from young naive cells functions well into old age, but memory generated from aged naive cells functions poorly
Haynes, L., Eaton, S. M., Burns, E. M., Randall, T. D., & Swain, S. L. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2433717100 · Cited by 270
Is immunosenescence infectious?
Pawelec, G., Akbar, A. N., Caruso, C., Effros, R. B., Grubeck‐Loebenstein, B., & Wikby, A. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.05.006 · Cited by 260 · cited 1×
“The long-term, repeated stimulation of the immune system (particularly of T cells) by viruses that induce latent persistent infections is thought to have an important role in immune senescenc”
Background
The Decline in B Lymphopoiesis in Aged Mice Reflects Loss of Very Early B-Lineage Precursors
Miller, J. P., & Allman, D. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.5.2326 · Cited by 255
Benign Monoclonal Gammapathy
WALDENSTRÖM, J. G. (1984) · Acta Medica Scandinavica · doi:10.1111/j.0954-6820.1984.tb05032.x · Cited by 248
Interleukin 2, but Not Other Common γ Chain–Binding Cytokines, Can Reverse the Defect in Generation of Cd4 Effector T Cells from Naive T Cells of Aged Mice
Haynes, L., Linton, P., Eaton, S. M., Tonkonogy, S. L., & Swain, S. L. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.190.7.1013 · Cited by 248
Age-related CD8 T Cell Clonal Expansions Constrict CD8 T Cell Repertoire and Have the Potential to Impair Immune Defense
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
Large Numbers of Dysfunctional CD8+ T Lymphocytes Bearing Receptors for a Single Dominant CMV Epitope in the Very Old
Ouyang, Q., Wagner, W. M., Wikby, A., Walter, S., Aubert, G., Dodi, A. I., Travers, P. J., & Pawelec, G. (2003) · Journal of Clinical Immunology · doi:10.1023/a:1024580531705 · Cited by 239
Age-associated accumulation of CMV-specific CD8+ T cells expressing the inhibitory killer cell lectin-like receptor G1 (KLRG1)
Ouyang, Q., Wagner, W. M., Voehringer, D., Wikby, A., Klatt, T., Walter, S., Müller, C. A., Pircher, H., & Pawelec, G. (2003) · Experimental Gerontology · doi:10.1016/s0531-5565(03)00134-7 · Cited by 238
IL-7 therapy dramatically alters peripheral T-cell homeostasis in normal and SIV-infected nonhuman primates
Fry, T. J. (2002) · Blood · doi:10.1182/blood-2002-07-2297 · Cited by 234
Lymphokines and aging: interleukin-2 production and activity in aged animals.
Thoman, M. L., & Weigle, W. O. (1981) · The Journal of Immunology · doi:10.4049/jimmunol.127.5.2102 · Cited by 232
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
Unexpected 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
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
The generation of protective memory-like CD8+ T cells during homeostatic proliferation requires CD4+ T cells
Hamilton, S. E., Wolkers, M. C., Schoenberger, S. P., & Jameson, S. C. (2006) · Nature Immunology · doi:10.1038/ni1326 · Cited by 218
Effects of Castration on Thymocyte Development in Two Different Models of Thymic Involution
Heng, T. S. P., Goldberg, G. L., Gray, D. H. D., Sutherland, J. S., Chidgey, A. P., & Boyd, R. L. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.5.2982 · Cited by 216 · cited 1×
“For example, 22-month-old mice have less than a tenth of the RTEs present in their young adult counterpart”
Background
Reduction in the Developmental Potential of Intrathymic T Cell Progenitors with Age
Min, H., Montecino-Rodriguez, E., & Dorshkind, K. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.1.245 · Cited by 216
The Immune System in the Elderly: Activation-Induced and Damage-Induced Apoptosis
Ginaldi, L., Martinis, M. D., Monti, D., & Franceschi, C. (2004) · Immunologic Research · doi:10.1385/ir:30:1:081 · Cited by 202
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 · cited 1×
“It remains unclear whether there is one crucial type of age-related change that results in a senescent cellular phenotype, or whether, perhaps more likely, numerous types of change jointly lead to such a phenotyp”
Background
Enrichment of Immediate-Early 1 (m123/pp89) Peptide-Specific CD8 T Cells in a Pulmonary CD62LloMemory-Effector Cell Pool during Latent Murine Cytomegalovirus Infection of the Lungs
Holtappels, R., Pahl-Seibert, M.-F., Thomas, D., & Reddehase, M. J. (2000) · Journal of Virology · doi:10.1128/jvi.74.24.11495-11503.2000 · Cited by 200
Efficient thymic immigration of B220+ lymphoid-restricted bone marrow cells with T precursor potential
Martin, C. H., Aifantis, I., Scimone, M. L., von Andrian, U. H., Reizis, B., von Boehmer, H., & Gounari, F. (2003) · Nature Immunology · doi:10.1038/ni965 · Cited by 200
IL-15 induces CD4+ effector memory T cell production and tissue emigration in nonhuman primates
Picker, L. J. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27564 · Cited by 195
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
PD-1 expression on human CD8 T cells depends on both state of differentiation and activation status
Sauce, D., Almeida, J. R., Larsen, M., Haro, L., Autran, B., Freeman, G. J., & Appay, V. (2007) · AIDS · doi:10.1097/qad.0b013e3282eee548 · Cited by 179
Age-associated thymic atrophy is linked to a decline in IL-7 production
Andrew, D. (2002) · Experimental Gerontology · doi:10.1016/s0531-5565(01)00213-3 · Cited by 170
A central role for thymic emigrants in peripheral T cell homeostasis
Berzins, S. P., Godfrey, D. I., Miller, J. F. A. P., & Boyd, R. L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.17.9787 · Cited by 163 · cited 1×
“However, this balance probably depends on the stable naive T-cell pool, which in turn requires the production of new T cells by the thymu”
Background
Inflammatory cytokines overcome age-related defects in CD4 T cell responses in vivo
Haynes, L., Eaton, S. M., Burns, E. M., Rincon, M., & Swain, S. L. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.9.5194 · Cited by 162
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 · cited 1×
“2a ); these changes have been described in detail elsewher”
Background
Genome-Wide Analysis Reveals a Highly Diverse CD8 T Cell Response to Murine Cytomegalovirus
Munks, M. W., Gold, M. C., Zajac, A. L., Doom, C. M., Morello, C. S., Spector, D. H., & Hill, A. B. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.6.3760 · Cited by 145 · cited 1×
“Second, the CD8 + T-cell response against CMV is unusually broad, targeting numerous viral peptide”
Background
Epstein–Barr virus-specific CD8+ T cells that re-express CD45RA are apoptosis-resistant memory cells that retain replicative potential
Dunne, P. J., Faint, J. M., Gudgeon, N. H., Fletcher, J. M., Plunkett, F. J., Soares, M. V. D., Hislop, A. D., Annels, N. E., Rickinson, A. B., Salmon, M., et al. (2002) · Blood · doi:10.1182/blood-2002-01-0160 · Cited by 144
Evolution of diverse antiviral CD8+ T cell populations after murine cytomegalovirus infection
Sierro, S. R., Rothkopf, R., & Klenerman, P. (2005) · European Journal of Immunology · doi:10.1002/eji.200425534 · Cited by 144
The immune S ystem in the elderly
Ginaldi, L., Martinis, M. D., D’Ostilio, A., Marini, L., Loreto, M. F., Martorelli, V., & Quaglino, D. (1999) · Immunologic Research · doi:10.1007/bf02786467 · Cited by 139
Altered IL-7Rα expression with aging and the potential implications of IL-7 therapy on CD8+ T-cell immune responses
Kim, H., Hong, M. S., Dan, J. M., & Kang, I. (2005) · Blood · doi:10.1182/blood-2005-09-3560 · Cited by 136
Two Antigenic Peptides from Genes m123 and m164 of Murine Cytomegalovirus Quantitatively Dominate CD8 T-Cell Memory in the H-2 d Haplotype
Holtappels, R., Thomas, D., Podlech, J., & Reddehase, M. J. (2002) · Journal of Virology · doi:10.1128/jvi.76.1.151-164.2002 · Cited by 133
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 · cited 1×
“We found that homeostatic proliferation of naive T cells in the blood of aged rhesus macaques inversely correlates with the number and proportion of naive T cells in these animals, and that this is not accompanied by an accumulation of these cells, but rather by their rapid turnove”
BackgroundSelf-citation
Single-Cell Analyses Reveal Two Defects in Peptide-Specific Activation of Naive T Cells from Aged Mice
Garcia, G. G., & Miller, R. A. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.5.3151 · Cited by 123
Reconstitution of CD8 T cells is essential for the prevention of multiple-organ cytomegalovirus histopathology after bone marrow transplantation.
Podlech, J., Reddehase, M. J., Holtappels, R., Steffens, H. P., & Wirtz, N. (1998) · Journal of General Virology · doi:10.1099/0022-1317-79-9-2099 · Cited by 123 · cited 1×
“Experiments showing that CD8 + T cells specific for some viral antigens accumulat”
Background
T-cell clonality in immune responses
Maini, M. K., Casorati, G., Dellabona, P., Wack, A., & Beverley, P. C. L. (1999) · Immunology Today · doi:10.1016/s0167-5699(99)01472-3 · Cited by 121 · cited 1×
“Several published manuscripts have described an accumulation of dysfunctional or hypofunctional cells with a 'terminally differentiated' phenotype that is associated with human agein”
Background
The immune S ystem in the elderly
Ginaldi, L., Martinis, M. D., D’Ostitio, A., Marini, L., Loreto, M. F., Corsi, M., & Quaglino, D. (1999) · Immunologic Research · doi:10.1007/bf02786466 · Cited by 115
Immunopathogenesis of herpetic ocular disease
Thomas, J., & Rouse, B. T. (1997) · Immunologic Research · doi:10.1007/bf02786400 · Cited by 114 · cited 1×
“Rather, the pathogen finds a niche where it establishes latency (for example, HSV establishes latent infection in neurons, mostly in the sensory ganglia innervating the site of viral entr”
Background
The immunogenicity of human and murine cytomegaloviruses
Reddehase, M. J. (2000) · Current Opinion in Immunology · doi:10.1016/s0952-7915(00)00106-0 · Cited by 113 · cited 1×
“This response also displays an unusual feature of progressive, long-term expansion of antigen-specific CD8 + memory T cell”
Background
The immune response of aged mice to influenza: Diminished T-cell proliferation, interleukin 2 production and cytotoxicity
Effros, R. B., & Walford, R. L. (1983) · Cellular Immunology · doi:10.1016/0008-8749(83)90237-x · Cited by 108 · cited 1×
“It is well accepted that IL-2 production decreases with agein”
Background
Influences of Dietary Restriction on Immunity to Influenza in Aged Mice
Effros, R. B., Walford, R. L., Weindruch, R. H., & Mitcheltree, C. (1991) · Journal of Gerontology · doi:10.1093/geronj/46.4.b142 · Cited by 105
IL-7 Gene Therapy in Aging Restores Early Thymopoiesis without Reversing Involution
Phillips, J. A., Brondstetter, T. I., English, C. A., Lee, H. E., Virts, E. L., & Thoman, M. L. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.8.4867 · Cited by 104 · cited 1×
“However, much remains to be understood about the in vivo action of exogenously administered cytokines, particularly from non-human primate and human clinical studie”
Background
T cell aging
Nikolich‐Žugich, J. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050341 · Cited by 103
Newly generated CD4 T cells in aged animals do not exhibit age-related defects in response to antigen
Haynes, L., Eaton, S. M., Burns, E. M., Randall, T. D., & Swain, S. L. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20041933 · Cited by 102
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
Human Immunodeficiency Virus Type 1 (HIV-1)-Specific CD8+TEMRACells in Early Infection Are Linked to Control of HIV-1 Viremia and Predict the Subsequent Viral Load Set Point
Northfield, J. W., Loo, C. P., Barbour, J. D., Spotts, G. E., Hecht, F. M., Klenerman, P., Nixon, D. F., & Michaëlsson, J. (2007) · Journal of Virology · doi:10.1128/jvi.00045-07 · Cited by 92
Immunity and age: living in the past?
Woodland, D. L., & Blackman, M. A. (2006) · Trends in Immunology · doi:10.1016/j.it.2006.05.002 · Cited by 84 · cited 1×
“Therefore, both the established pathogens (such as influenza virus, pneumococcus and varicella-zoster virus (VZV)) and the newly emerging pathogens (such as West Nile virus (WNV) and severe acute respiratory syndrome (SARS)-associated coronavirus) take a disproportionate and heavy toll in sick days and deaths in the e…”
Background
Immunosenescence: a problem of lymphopoiesis, homeostasis, microenvironment, and signaling
Cambier, J. C. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00276.x · Cited by 83
Physiology of aging
Masoro, E. J. (2001) · International Journal of Sport Nutrition and Exercise Metabolism · doi:10.1123/ijsnem.11.s1.s218 · Cited by 81
The Role of Interleukin-6 in Certain Age-Related Diseases
Ershler, W. B., Sun, W., & Binkley, N. (1994) · Drugs & Aging · doi:10.2165/00002512-199405050-00005 · Cited by 80
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 · cited 1×
“Secondary changes then ensue from a compensatory homeostatic T-cell expansion that attempts to maintain the size of the naive T-cell compartmen”
Background
Phenotypic and functional T-cell aging in rhesus macaques (Macaca mulatta): differential behavior of CD4 and CD8 subsets
Janković, V., Messaoudi, I., & Nikolich‐Žugich, J. (2003) · Blood · doi:10.1182/blood-2003-03-0927 · Cited by 75 · cited 1×
“Second, similar T-cell populations in non-human primates, although possibly hyporesponsive in vitro , appear to turn over quite vigorously in vivo , as measured by labelling with bromodeoxyuridine”
Background
A dose effect of IL-7 on thymocyte development
Kassar, N. E., Lucas, P. J., Klug, D. B., Zamisch, M., Merchant, M. S., Bare, C. V., Choudhury, B., Sharrow, S. O., Richie, E. R., Mackall, C. L., et al. (2004) · Blood · doi:10.1182/blood-2004-01-0201 · Cited by 75
Recombinant Interleukin-7 Induces Proliferation of Naive Macaque CD4+and CD8+T Cells In Vivo
Moniuszko, 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
Development and Migration of Protective CD8+ T Cells into the Nervous System following Ocular Herpes Simplex Virus-1 Infection
Lang, A. M., & Nikolich‐Žugich, J. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.5.2919 · Cited by 71
Herpesvirus Evasion of the Immune System
Johnson, D. C., & Hill, A. B. (1998) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-72045-1_8 · Cited by 68
The Putative Natural Killer Decoy Early Genem04(gp34) of Murine Cytomegalovirus Encodes an Antigenic Peptide Recognized by Protective Antiviral CD8 T Cells
Holtappels, R., Thomas, D., Podlech, J., Geginat, G., Steffens, H.-P., & Reddehase, M. J. (2000) · Journal of Virology · doi:10.1128/jvi.74.4.1871-1884.2000 · Cited by 65
Age influence on the thymic capacity to promote differentiation of T cells: Induction of different composition of T cell subsets by aging thymus
Utsuyama, M., Kasai, M., Kurashima, C., & Hirokawa, K. (1991) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(91)90098-k · Cited by 60 · cited 1×
“That, however, does not exclude possible defects in thymic stromal component”
Background
Dancing with the enemy: the interplay of herpes simplex virus with dendritic cells
Novak, N., & Peng, W. (2005) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2005.02927.x · Cited by 60
Delayed Immune Aging in Diet-Restricted B6CBAT6 Fl Mice Is Associated With Preservation of Naive T Cells
Chen, J., Astle, C. M., & Harrison, D. E. (1998) · The Journals of Gerontology Series A · doi:10.1093/gerona/53a.5.b330 · Cited by 57
Molecular, Cellular, and Antigen Requirements for Development of Age-Associated T Cell Clonal Expansions In Vivo
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
Age-Related CD8+ T Cell Clonal Expansions Express Elevated Levels of CD122 and CD127 and Display Defects in Perceiving Homeostatic Signals
Messaoudi, I., Warner, J., & Nikolich‐Žugich, J. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.5.2784 · Cited by 53
Immune evasion by gamma-herpesviruses
Stevenson, P. G. (2004) · Current Opinion in Immunology · doi:10.1016/j.coi.2004.05.002 · Cited by 53 · cited 1×
“Herpesviruses usually establish latency in specific cell types or tissues and deploy multiple mechanisms to evade the innate and adaptive immune system”
Background
The defects in effector generation associated with aging can be reversed by addition of IL-2 but not other related γc-receptor binding cytokines
Haynes, L., Eaton, S. M., & Swain, S. L. (2000) · Vaccine · doi:10.1016/s0264-410x(99)00501-0 · Cited by 53
Reevaluating current models of thymic involution
Montecino‐Rodriguez, E., Min, H., & Dorshkind, K. A. (2005) · Seminars in Immunology · doi:10.1016/j.smim.2005.05.006 · Cited by 50
Antigen-Specific CD8+ T Cell Clonal Expansions Develop from Memory T Cell Pools Established by Acute Respiratory Virus Infections
Ely, K. H., Ahmed, M., Kohlmeier, J. E., Roberts, A. D., Wittmer, S. T., Blackman, M. A., & Woodland, D. L. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.6.3535 · Cited by 50
Age-Related Dysregulation of CD8+ T Cell Memory Specific for a Persistent Virus Is Independent of Viral Replication
Lang, 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
T cells in aging mice: genetic, developmental, and biochemical analyses
Miller, R. A., Berger, S. B., Burke, D., Gałecki, A. T., Garcia, G. G., Harper, J. M., & Akha, A. A. S. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00254.x · Cited by 41 · cited 1×
“2a ); these changes have been described in detail elsewher”
Background
Aging and T cell development: Interplay between progenitors and their environment
Zediak, V. P., & Bhandoola, A. (2005) · Seminars in Immunology · doi:10.1016/j.smim.2005.05.004 · Cited by 39
Large scale analysis of pediatric antiviral CD8+ T cell populations reveals sustained, functional and mature responses
Komatsu, H., Inui, A., Sogo, T., Fujisawa, T., Nagasaka, H., Nonoyama, S., Sierro, S. R., Northfield, J. W., Lucas, M., Vargas, A., et al. (2006) · Immunity & Ageing · doi:10.1186/1742-4933-3-11 · Cited by 38
Is immune senescence reversible?
Beverley, P. C. L., & Grubeck-Loebenstein, B. (2000) · Vaccine · doi:10.1016/s0264-410x(99)00514-9 · Cited by 35 · cited 1×
“Therefore, they have been termed T effector memory, re-expressing CD45RA (or T-EMRA) cell”
Background
Approaches to improved influenza vaccination
Betts, R. F., & Treanor, J. J. (2000) · Vaccine · doi:10.1016/s0264-410x(99)00508-3 · Cited by 34
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
Naïve to memory T-cell differentiation during homeostasis-driven proliferation
Ge, Q., Hu, H., Eisen, H. N., & Chen, J. (2002) · Microbes and Infection · doi:10.1016/s1286-4579(02)01572-1 · Cited by 32
Cellular Senescence, Epigenetic Switches and c-Myc
Guney, I., & Sedivy, J. M. (2006) · Cell Cycle · doi:10.4161/cc.5.20.3348 · Cited by 30
The road to recovery: translating PD-1 biology into clinical benefit
Riley, J. L., & June, C. H. (2006) · Trends in Immunology · doi:10.1016/j.it.2006.12.001 · Cited by 30
Can we say that senescent cells cause ageing?
Bird, J., Ostler, E. L., & Faragher, R. (2003) · Experimental Gerontology · doi:10.1016/j.exger.2003.09.011 · Cited by 30 · cited 1×
“It remains unclear whether there is one crucial type of age-related change that results in a senescent cellular phenotype, or whether, perhaps more likely, numerous types of change jointly lead to such a phenotyp”
Background
Antigen Presentation in the Immune Response to Infectious Diseases
Pamer, E. G. (1999) · Clinical Infectious Diseases · doi:10.1086/515207 · Cited by 23 · cited 1×
“Defects that are not as well understood occur in antigen processing and presentatio”
Background
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 · cited 1×
“However, much remains to be understood about the in vivo action of exogenously administered cytokines, particularly from non-human primate and human clinical studie”
Background
Stemming the tide of thymic aging
Chidgey, A. P., & Boyd, R. L. (2006) · Nature Immunology · doi:10.1038/ni1006-1013 · Cited by 18 · cited 1×
“, which are potentially precipitated by factors that include sex hormone”
Background
Memories are made of this: synergy of T cell receptor and cytokine signals in CD4+ central memory cell survival
Caserta, S., & Zamoyska, R. (2007) · Trends in Immunology · doi:10.1016/j.it.2007.04.006 · Cited by 17
Limiting dilution analysis of IL-2 production: studies of age, genotype, and regulatory interactions.
Miller, R., & Stutman, O. (1982) · PubMed · Cited by 8
Giving T cells a chance to come back
Zúñiga‐Pflücker, J. C., & van den Brink, M. R. M. (2007) · Seminars in Immunology · doi:10.1016/j.smim.2007.11.001 · Cited by 7
Bone marrow transplantation from a pediatric donor with a high frequency of cytomegalovirus-specific T-cells
Komatsu, H., Kogawa, K., Nonoyama, S., Inui, A., Sogo, T., Fujisawa, T., & Klenerman, P. (2006) · Journal of Medical Virology · doi:10.1002/jmv.20746 · Cited by 6 · cited 1×
“Of note, children and young adults often mount strong CMV-specific immune response”
Background
Occurrence of a Carrier State for Herpesvirus tamarinus in Marmosets
Murphy, B. L., Maynard, J. E., Krushak, D. H., & Fields, R. M. (1971) · Applied Microbiology · doi:10.1128/am.21.1.50-52.1971 · Cited by 5

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Mocarski, E. S. & Courcelle, C. T. Cytomegaloviruses and their replication, in Fields Virology 4th edn (eds Knipe, D. M. & Howley, P. M.) 2629–2674 (Lippincot Williams & Wilkins, Philadelphia, 2001).
Pass, R. F. Cytomegalovirus, in Fields Virology 4th edn (eds Knipe, D. M. & Howley, P. M.) 2675–2706 (Lippincot Williams & Wilkins, Philadelphia, 2001).

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The role of senescent cells in ageing
van Deursen, J. M. (2014) · Nature · doi:10.1038/nature13193 · Cited by 2,623
A guide to vaccinology: from basic principles to new developments
Pollard, A. J., & Bijker, E. M. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-020-00479-7 · Cited by 1,593
Redefining Chronic Viral Infection
Virgin, H. W., Wherry, E. J., & Ahmed, R. (2009) · Cell · doi:10.1016/j.cell.2009.06.036 · Cited by 1,031
Immunosenescence: molecular mechanisms and diseases
Liu, Z., Liang, Q., Ren, Y., Guo, C., Ge, X., Wang, L., Cheng, Q., Luo, P., Zhang, Y., & Han, X. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01451-2 · Cited by 1,082
“Persistent antigen stimulation and stress-induced damage Numerous discoveries have generated a consensus that the antigen burden to which individuals are exposed during their lifetime is linked to immunosenescence.(60) Khan et al.”
Background
The aging of the immune system
Weiskopf, D., Weinberger, B., & Grubeck-Loebenstein, B. (2009) · Transplant International · doi:10.1111/j.1432-2277.2009.00927.x · Cited by 908

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Authors: Nikolich-Žugich, J.
Venue: Nature reviews. Immunology
Publisher: Springer Science and Business Media LLC
Published: 2008-07
Volume: 8
Issue: 7
Pages: 512-522
ISSN: 1474-1733 (ISSN-L)
1474-1741
DOI: 10.1038/nri2318
PMC: PMC5573867
OpenAlex: W1926141441
Cited by: 463
References: 128
Citations by year: 2026: 23 · 2025: 28 · 2024: 18 · 2023: 26 · 2022: 28 · 2021: 30 · 2020: 24 · 2019: 17 · 2018: 28 · 2017: 20 · 2016: 21 · 2015: 24 · 2014: 35 · 2013: 35 · 2012: 23
FWCI: 2.05
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
www.springer.com/tdm (tdm)
Locations: Nature reviews. Immunology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (n01ai50027-8-0-1)
U.S. Public Health Service (N01 50027)
National Institute on Aging (AG 20719, AG23664, P01AG023664, AG 21384, R01AG020719, U01AG021384, R37AG020719)
National Institute of Allergy and Infectious Diseases (N01 AI050027)
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 › Cell Biology › Telomeres, Telomerase, and Senescence
Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
Keywords: immunosenescence, T cell homeostasis, T cell subsets, persistent viruses, T cell receptor repertoire, aging
MeSH terms: Aging, Animals, Cell Differentiation, Herpes Simplex, Homeostasis, Humans, Infections, Receptors, Antigen, T-Cell, Thymus Gland, T-Lymphocyte Subsets, Cellular Senescence

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Ageing and life-long maintenance of T-cell subsets in the face of latent persistent infections.

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