When aging reaches CD4+ T-cells: Phenotypic and functional changes

Frontiers in Immunology

Volumn 4, Issue MAY, 2013, Pages

  Moro García, Marco Antonio ^a   Alonso Arias, Rebeca ^a   López Larrea, Carlos ^a,b  

^a HOSPITAL UNIVERSITARIO CENTRAL DE ASTURIAS   (Spain)

^b Section of Nephrology   (Spain)

Author keywords

CMV; IL 15; Immunosenescence; Inflammation; NKRs; T cells

Indexed keywords

CD16 ANTIGEN; CD27 ANTIGEN; CD28 ANTIGEN; CD40 LIGAND; CD45RA ANTIGEN; CD56 ANTIGEN; CD94 ANTIGEN; CHEMOKINE RECEPTOR CCR7; GAMMA INTERFERON; GRANZYME B; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 15; INTERLEUKIN 2; INTERLEUKIN 2 RECEPTOR; INTERLEUKIN 21; INTERLEUKIN 4; INTERLEUKIN 5; INTERLEUKIN 6; INTERLEUKIN 7; INTERLEUKIN 7 RECEPTOR; INTERLEUKIN 8; JANUS KINASE; L SELECTIN; PERFORIN; REACTIVE OXYGEN METABOLITE; STAT5 PROTEIN; T LYMPHOCYTE RECEPTOR; TUMOR NECROSIS FACTOR ALPHA; UNINDEXED DRUG;

AGING; AUTOIMMUNITY; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL DIFFERENTIATION; CELL PROLIFERATION; CYTOTOXICITY; DNA METHYLATION; HELPER CELL; HUMAN; IMMUNE DEFICIENCY; IMMUNE RESPONSE; IMMUNOLOGICAL MEMORY; MORTALITY; PROTEIN EXPRESSION; PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION; THYMUS; VIRUS INFECTION;

EID: 84883818596     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2013.00107     Document Type: Review

References (141)

1. Abedin, S., Michel, J. J., Lemster, B., and Vallejo, A. N. (2005). Diversity of NKR expression in aging T cells and in T cells of the aged: the new frontier into the exploration of protective immunity in the elderly. Exp. Gerontol. 40, 537-548.
2. Aiello, A. E., Haan, M., Blythe, L., Moore, K., Gonzalez, J. M., and Jagust, W. (2006). The influence of latent viral infection on rate of cognitive decline over 4 years. J. Am. Geriatr. Soc. 54, 1046-1054.
3. Alcami, A., and Koszinowski, U. H. (2000). Viral mechanisms of immune evasion. Immunol. Today 21, 447-455.
4. Almanzar, G., Schwaiger, S., Jenewein, B., Keller, M., Herndler-Brandstetter, D., Wurzner, R., et al. (2005). 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. J. Virol. 79, 3675-3683.
5. 4+ T cell numbers. J. Immunol. 169, 4850-4860.
6. 4+ T cells in HIV-infected patients with worse prognostic factors. J. Acquir. Immune Defic. Syndr. 51, 390-398.
7. 4+ T lymphocytes as a marker of senescence in the aged immune system. Age (Dordr.) 33, 591-605.
8. 28+ T cells. Aging Cell 10, 844-852.
9. Alonso-Arias, R., Moro-Garcia, M. A., Echeverria, A., Solano-Jaurrieta, J. J., Suarez-Garcia, F. M., and Lopez-Larrea, C. (2013). Intensity of the humoral response to Cytomegalovirus is associated with the phenotypic and functional status of the immune system. J. Virol. 87, 4486-4495.
10. 4+ T cell response to Epstein-Barr virus during primary and persistent infection. J. Exp. Med. 198, 903-911.
11. Andrews, N. P., Fujii, H., Goronzy, J. J., and Weyand, C. M. (2010). Telomeres and immunological diseases of aging. Gerontology 56, 390-403.
12. Appay, V., Dunbar, P. R., Callan, M., Klenerman, P., Gillespie, G. M., Papagno, L., et al. (2002a). Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections. Nat. Med. 8, 379-385.
13. 4(+) CTLs ex vivo. J. Immunol. 168, 5954-5958.
14. Appay, V., van Lier, R. A., Sallusto, F., and Roederer, M. (2008). Phenotype and function of human T lymphocyte subsets: consensus and issues. Cytometry A 73, 975-983.
15. Aronson, M. (1991). Hypothesis: involution of the thymus with aging - programmed and beneficial. Thymus 18, 7-13.
16. Aspinall, R. (1997). Age-associated thymic atrophy in the mouse is due to a deficiency affecting rearrangement of the TCR during intrathymic T cell development. J. Immunol. 158, 3037-3045.
17. 4+ T cells from HIV-infected persons and is inversely associated with aging. J. Infect. Dis. 199, 1019-1028.
18. 4+ T cells. PLoS Pathog. 7:e1002288. doi:10.1371/journal.ppat.1002288
19. Boyman, O., Krieg, C., Homann, D., and Sprent, J. (2012). Homeostatic maintenance of T cells and natural killer cells. Cell. Mol. Life Sci. 69, 1597-1608.
20. Bradley, B. A. (2002). Rejection and recipient age. Transpl. Immunol. 10, 125-132.
21. Brocker, T. (1997). Survival of mature CD4 T lymphocytes is dependent on major histocompatibility complex class II-expressing dendritic cells. J. Exp. Med. 186, 1223-1232.
22. Brown, D. M., Lee, S., Garcia-Hernandez, M. D., and Swain, S. L. (2012). Multi-functional CD4 cells expressing IFN-gamma and perforin mediate protection against lethal influenza infection. J. Virol. 86, 6792-6803.
23. Bryl, E., and Witkowski, J. M. (2004). Decreased proliferative capability of CD4(+) cells of elderly people is associated with faster loss of activation-related antigens and accumulation of regulatory T cells. Exp. Gerontol. 39, 587-595.
24. Campbell, J. J., Bowman, E. P., Murphy, K., Youngman, K. R., Siani, M. A., Thompson, D. A., et al. (1998). 6-C-kine (SLC), a lymphocyte adhesion-triggering chemokine expressed by high endothelium, is an agonist for the MIP-3beta receptor CCR7. J. Cell Biol. 141, 1053-1059.
25. Campbell, J. J., Murphy, K. E., Kunkel, E. J., Brightling, C. E., Soler, D., Shen, Z., et al. (2001). CCR7 expression and memory T cell diversity in humans. J. Immunol. 166, 877-884.
26. Caruso, C., Candore, G., Cigna, D., DiLorenzo, G., Sireci, G., Dieli, F., et al. (1996). Cytokine production pathway in the elderly. Immunol. Res. 15, 84-90.
27. Chiu, W. K., Fann, M., and Weng, N. P. (2006). Generation and growth of CD28nullCD8+ memory T cells mediated by IL-15 and its induced cytokines. J. Immunol. 177, 7802-7810.
28. Choi, J., Fauce, S. R., and Effros, R. B. (2008). Reduced telomerase activity in human T lymphocytes exposed to cortisol. Brain Behav. Immun. 22, 600-605.
29. Czesnikiewicz-Guzik, M., Lee, W. W., Cui, D., Hiruma, Y., Lamar, D. L., Yang, Z. Z., et al. (2008). T cell subset-specific susceptibility to aging. Clin. Immunol. 127, 107-118.
30. Dace, D. S., and Apte, R. S. (2008). Effect of senescence on macrophage polarization and angiogenesis. Rejuvenation Res. 11, 177-185.
31. Dagarag, M., Evazyan, T., Rao, N., and Effros, R. B. (2004). Genetic manipulation of telomerase in HIV-specific CD8+ T cells: enhanced antiviral functions accompany the increased proliferative potential and telomere length stabilization. J. Immunol. 173, 6303-6311.
32. De Martinis, M., Franceschi, C., Monti, D., and Ginaldi, L. (2006). Inflammation markers predicting frailty and mortality in the elderly. Exp. Mol. Pathol. 80, 219-227.
33. De Rosa, S. C., Herzenberg, L. A., Herzenberg, L. A., and Roederer, M. (2001). 11-Color, 13-parameter flow cytometry: identification of human naive T cells by phenotype, function, and T-cell receptor diversity. Nat. Med. 7, 245-248.
34. DelaRosa, O., Pawelec, G., Peralbo, E., Wikby, A., Mariani, E., Mocchegiani, E., et al. (2006). Immunological biomarkers of ageing in man: changes in both innate and adaptive immunity are associated with health and longevity. Biogerontology 7, 471-481.
35. den Braber, I., Mugwagwa, T., Vrisekoop, N., Westera, L., Mogling, R., de Boer, A. B., et al. (2012). Maintenance of peripheral naive T cells is sustained by thymus output in mice but not humans. Immunity 36, 288-297.
36. Deng, Y., Jing, Y., Campbell, A. E., and Gravenstein, S. (2004). Age-related impaired type 1 T cell responses to influenza: reduced activation ex vivo, decreased expansion in CTL culture in vitro, and blunted response to influenza vaccination in vivo in the elderly. J. Immunol. 172, 3437-3446.
37. Derhovanessian, E., Larbi, A., and Pawelec, G. (2009). Biomarkers of human immunosenescence: impact of Cytomegalovirus infection. Curr. Opin. Immunol. 21, 440-445.
38. 4+CD45RA+CD27- memory T cells. J. Immunol. 187, 2093-2100.
39. Dorshkind, K., Montecino-Rodriguez, E., and Signer, R. A. (2009). The ageing immune system: is it ever too old to become young again? Nat. Rev. Immunol. 9, 57-62.
40. Dowling, M. R., and Hodgkin, P. D. (2009). Why does the thymus involute? A selection-based hypothesis. Trends Immunol. 30, 295-300.
41. 28 null T cells in coronary artery disease: when helpers become killers. Cardiovasc. Res. 81, 11-19.
42. Ferrucci, L., Corsi, A., Lauretani, F., Bandinelli, S., Bartali, B., Taub, D. D., et al. (2005). The origins of age-related proinflammatory state. Blood 105, 2294-2299.
43. 4+ T cells in healthy carriers are continuously driven to replicative exhaustion. J. Immunol. 175, 8218-8225.
44. Forsey, R. J., Thompson, J. M., Ernerudh, J., Hurst, T. L., Strindhall, J., Johansson, B., et al. (2003). Plasma cytokine profiles in elderly humans. Mech. Ageing Dev. 124, 487-493.
45. Forster, R., Schubel, A., Breitfeld, D., Kremmer, E., Renner-Muller, I., Wolf, E., et al. (1999). CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs. Cell 99, 23-33.
46. Franceschi, C., Capri, M., Monti, D., Giunta, S., Olivieri, F., Sevini, F., et al. (2007). Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech. Ageing Dev. 128, 92-105.
47. Franceschi, C., Valensin, S., Bonafe, M., Paolisso, G., Yashin, A. I., Monti, D., et al. (2000). The network and the remodeling theories of aging: historical background and new perspectives. Exp. Gerontol. 35, 879-896.
48. Fritsch, R. D., Shen, X., Sims, G. P., Hathcock, K. S., Hodes, R. J., and Lipsky, P. E. (2005). Stepwise differentiation of CD4 memory T cells defined by expression of CCR7 and CD27. J. Immunol. 175, 6489-6497.
49. 4+ T cells in protection against CMV disease. Blood 101, 2686-2692.
50. Geginat, J., Sallusto, F., and Lanzavecchia, A. (2001). Cytokine-driven proliferation and differentiation of human naive, central memory, and effector memory CD4(+) T cells. J. Exp. Med. 194, 1711-1719.
51. 4+CD28null T-lymphocytes in diabetic patients: exploring new pathogenetic mechanisms of increased cardiovascular risk in diabetes mellitus. Eur. Heart J. 32, 1214-1226.
52. Giunta, B., Fernandez, F., Nikolic, W. V., Obregon, D., Rrapo, E., Town, T., et al. (2008). Inflammaging as a prodrome to Alzheimer's disease. J. Neuroinflammation 5, 51.
53. 28-CD8 T cells mediated by interleukin 15. Exp. Gerontol. 42, 412-415.
54. Goronzy, J. J., Lee, W. W., and Weyand, C. M. (2007). Aging and T-cell diversity. Exp. Gerontol. 42, 400-406.
55. Griffin, W. S. (2006). Inflammation and neurodegenerative diseases. Am. J. Clin. Nutr. 83, 470S-474S.
56. Grundemann, C., Bauer, M., Schweier, O., von Oppen, N., Lassing, U., Saudan, P., et al. (2006). Cutting edge: identification of E-cadherin as a ligand for the murine killer cell lectin-like receptor G1. J. Immunol. 176, 1311-1315.
57. Hadrup, S. R., Strindhall, J., Kollgaard, T., Seremet, T., Johansson, B., Pawelec, G., et al. (2006). 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. J. Immunol. 176, 2645-2653.
58. Hambrecht, R., Wolf, A., Gielen, S., Linke, A., Hofer, J., Erbs, S., et al. (2000). Effect of exercise on coronary endothelial function in patients with coronary artery disease. N. Engl. J. Med. 342, 454-460.
59. Harari, A., Vallelian, F., Meylan, P. R., and Pantaleo, G. (2005). Functional heterogeneity of memory CD4 T cell responses in different conditions of antigen exposure and persistence. J. Immunol. 174, 1037-1045.
60. Harkins, L., Volk, A. L., Samanta, M., Mikolaenko, I., Britt, W. J., Bland, K. I., et al. (2002). Specific localisation of human Cytomegalovirus nucleic acids and proteins in human colorectal cancer. Lancet 360, 1557-1563.
61. Hayhoe, R. P., Henson, S. M., Akbar, A. N., and Palmer, D. B. (2010). Variation of human natural killer cell phenotypes with age: identification of a unique KLRG1-negative subset. Hum. Immunol. 71, 676-681.
62. Haynes, L., and Maue, A. C. (2009). Effects of aging on T cell function. Curr. Opin. Immunol. 21, 414-417.
63. Henson, S. M., Franzese, O., Macaulay, R., Libri, V., Azevedo, R. I., Kiani-Alikhan, S., et al. (2009). KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells. Blood 113, 6619-6628.
64. Hodes, R. J., Hathcock, K. S., and Weng, N. P. (2002). Telomeres in T and B cells. Nat. Rev. Immunol. 2, 699-706.
65. Johnston, J. A., Bacon, C. M., Riedy, M. C., and O'Shea, J. J. (1996). Signaling by IL-2 and related cytokines: JAKs, STATs, and relationship to immunodeficiency. J. Leukoc. Biol. 60, 441-452.
66. Kimmig, S., Przybylski, G. K., Schmidt, C. A., Laurisch, K., Mowes, B., Radbruch, A., et al. (2002). Two subsets of naive T helper cells with distinct T cell receptor excision circle content in human adult peripheral blood. J. Exp. Med. 195, 789-794.
67. King, D. E., Carek, P., Mainous, A. G. III, and Pearson, W. S. (2003). Inflammatory markers and exercise: differences related to exercise type. Med. Sci. Sports Exerc. 35, 575-581.
68. Klapper, W., Qian, W., Schulte, C., and Parwaresch, R. (2003). DNA damage transiently increases TRF2 mRNA expression and telomerase activity. Leukemia 17, 2007-2015.
69. Koch, S., Larbi, A., Derhovanessian, E., Ozcelik, D., Naumova, E., and Pawelec, G. (2008). Multiparameter flow cytometric analysis of CD4 and CD8 T cell subsets in young and old people. Immun. Ageing 5, 6.
70. Kutza, A. S., Muhl, E., Hackstein, H., Kirchner, H., and Bein, G. (1998). High incidence of active Cytomegalovirus infection among septic patients. Clin. Infect. Dis. 26, 1076-1082.
71. Lacorazza, H. D., Guevara Patino, J. A., Weksler, M. E., Radu, D., and Nikolic-Zugic, J. (1999). Failure of rearranged TCR transgenes to prevent age-associated thymic involution. J. Immunol. 163, 4262-4268.
72. Lautenschlager, N. T., Cox, K., and Cyarto, E. V. (2011). The influence of exercise on brain ageing and dementia. Biochim. Biophys. Acta. 1822, 474-481.
73. Le Garff-Tavernier, M., Beziat, V., Decocq, J., Siguret, V., Gandjbakhch, F., Pautas, E., et al. (2010). Human NK cells display major phenotypic and functional changes over the life span. Aging Cell 9, 527-535.
74. 4+T cell memory. Proc. Natl. Acad. Sci. U.S.A. 101, 9357-9362.
75. Libby, P., Ridker, P. M., and Maseri, A. (2002). Inflammation and atherosclerosis. Circulation 105, 1135-1143.
76. Lio, D., Candore, G., Crivello, A., Scola, L., Colonna-Romano, G., Cavallone, L., et al. (2004). Opposite effects of interleukin 10 common gene polymorphisms in cardiovascular diseases and in successful ageing: genetic background of male centenarians is protective against coronary heart disease. J. Med. Genet. 41, 790-794.
77. Liu, Y., Kuick, R., Hanash, S., and Richardson, B. (2009). DNA methylation inhibition increases T cell KIR expression through effects on both promoter methylation and transcription factors. Clin. Immunol. 130, 213-224.
78. Lu, Q., Wu, A., Ray, D., Deng, C., Attwood, J., Hanash, S., et al. (2003). DNA methylation and chromatin structure regulate T cell perforin gene expression. J. Immunol. 170, 5124-5132.
79. Lynch, H. E., Goldberg, G. L., Chidgey, A., Van den Brink, M. R., Boyd, R., and Sempowski, G. D. (2009). Thymic involution and immune reconstitution. Trends Immunol. 30, 366-373.
80. 4(+) T cells in healthy humans. J. Exp. Med. 200, 255-260.
81. Mari, D., Mannucci, P. M., Coppola, R., Bottasso, B., Bauer, K. A., and Rosenberg, R. D. (1995). Hypercoagulability in centenarians: the paradox of successful aging. Blood 85, 3144-3149.
82. Melzer, K., Kayser, B., and Pichard, C. (2004). Physical activity: the health benefits outweigh the risks. Curr. Opin. Clin. Nutr. Metab. Care 7, 641-647.
83. Moro-Garcia, M. A., Alonso-Arias, R., Lopez-Vazquez, A., Suarez-Garcia, F. M., Solano-Jaurrieta, J. J., Baltar, J., et al. (2012). Relationship between functional ability in older people, immune system status, and intensity of response to CMV. Age (Dordr.) 34, 479-495.
84. Naylor, K., Li, G., Vallejo, A. N., Lee, W. W., Koetz, K., Bryl, E., et al. (2005). The influence of age on T cell generation and TCR diversity. J. Immunol. 174, 7446-7452.
85. Nikolich-Zugich, J. (2005). T cell aging: naive but not young. J. Exp. Med. 201, 837-840.
86. Nikolich-Zugich, J. (2008). Ageing and life-long maintenance of T-cell subsets in the face of latent persistent infections. Nat. Rev. Immunol. 8, 512-522.
87. O'Leary, J. J., and Hallgren, H. M. (1991). Aging and lymphocyte function: a model for testing gerontologic hypotheses of aging in man. Arch. Gerontol. Geriatr. 12, 199-218.
88. Olsson, J., Wikby, A., Johansson, B., Lofgren, S., Nilsson, B. O., and Ferguson, F. G. (2000). Age-related change in peripheral blood T-lymphocyte subpopulations and Cytomegalovirus infection in the very old: the Swedish longitudinal OCTO immune study. Mech. Ageing Dev. 121, 187-201.
89. Pawelec, G., and Derhovanessian, E. (2010). Role of CMV in immune senescence. Virus Res. 157, 175-179.
90. Pedersen, B. K., and Saltin, B. (2006). Evidence for prescribing exercise as therapy in chronic disease. Scand. J. Med. Sci. Sports 16(Suppl. 1), 3-63.
91. Pellicano, M., Larbi, A., Goldeck, D., Colonna-Romano, G., Buffa, S., Bulati, M., et al. (2012). Immune profiling of Alzheimer patients. J. Neuroimmunol. 242, 52-59.
92. Perillo, N. L., Walford, R. L., Newman, M. A., and Effros, R. B. (1989). Human T lymphocytes possess a limited in vitro life span. Exp. Gerontol. 24, 177-187.
93. Posnett, D. N., Sinha, R., Kabak, S., and Russo, C. (1994). Clonal populations of T cells in normal elderly humans: the T cell equivalent to "benign monoclonal gammapathy". J. Exp. Med. 179, 609-618.
94. Pradhan, A. D., Manson, J. E., Rifai, N., Buring, J. E., and Ridker, P. M. (2001). C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 286, 327-334.
95. Prelog, M. (2006). Aging of the immune system: a risk factor for autoimmunity? Autoimmun. Rev. 5, 136-139.
96. Prlic, M., and Jameson, S. C. (2002). Homeostatic expansion versus antigen-driven proliferation: common ends by different means? Microbes Infect. 4, 531-537.
97. Prosch, S., Wendt, C. E., Reinke, P., Priemer, C., Oppert, M., Kruger, D. H., et al. (2000). A novel link between stress and human Cytomegalovirus (HCMV) infection: sympathetic hyperactivity stimulates HCMV activation. Virology 272, 357-365.
98. 4+ memory T cells are IL-15 dependent. J. Exp. Med. 204, 951-961.
99. Raison, C. L., Capuron, L., and Miller, A. H. (2006). Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 27, 24-31.
100. 28null T lymphocytes by tumor necrosis factor-alpha blockade in patients with unstable angina. Circulation 113, 2272-2277.
101. Sallusto, F., Lenig, D., Forster, R., Lipp, M., and Lanzavecchia, A. (1999). Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 401, 708-712.
102. Sauce, D., Larsen, M., Fastenackels, S., Duperrier, A., Keller, M., Grubeck-Loebenstein, B., et al. (2009). Evidence of premature immune aging in patients thymectomized during early childhood. J. Clin. Invest. 119, 3070-3078.
103. 28(-) T cell clonal expansions and an imbalance in the production of Th1 and Th2 cytokines. J. Immunol. 168, 5893-5899.
104. Seder, R. A., Darrah, P. A., and Roederer, M. (2008). T-cell quality in memory and protection: implications for vaccine design. Nat. Rev. Immunol. 8, 247-258.
105. Simanek, A. M., Dowd, J. B., and Aiello, A. E. (2009). Persistent pathogens linking socioeconomic position and cardiovascular disease in the US. Int. J. Epidemiol. 38, 775-787.
106. Smeltz, R. B. (2007). Profound enhancement of the IL-12/IL-18 pathway of IFN-gamma secretion in human CD8+ memory T cell subsets via IL-15. J. Immunol. 178, 4786-4792.
107. Speelman, A. D., van de Warrenburg, B. P., van Nimwegen, M., Petzinger, G. M., Munneke, M., and Bloem, B. R. (2011). How might physical activity benefit patients with Parkinson disease? Nat. Rev. Neurol. 7, 528-534.
108. Stowe, R. P., Kozlova, E. V., Yetman, D. L., Walling, D. M., Goodwin, J. S., and Glaser, R. (2007). Chronic herpesvirus reactivation occurs in aging. Exp. Gerontol. 42, 563-570.
109. Strindhall, J., Skog, M., Ernerudh, J., Bengner, M., Lofgren, S., Matussek, A., et al. (2012). The inverted CD4/CD8 ratio and associated parameters in 66-year-old individuals: the Swedish HEXA immune study. Age (Dordr.) 35, 985-991.
110. Surh, C. D., and Sprent, J. (2008). Homeostasis of naive and memory T cells. Immunity 29, 848-862.
111. Swainson, L., Verhoeyen, E., Cosset, F. L., and Taylor, N. (2006). IL-7R alpha gene expression is inversely correlated with cell cycle progression in IL-7-stimulated T lymphocytes. J. Immunol. 176, 6702-6708.
112. Swigut, T., Shohdy, N., and Skowronski, J. (2001). Mechanism for down-regulation of CD28 by Nef. EMBO J. 20, 1593-1604.
113. Tan, J. T., Dudl, E., LeRoy, E., Murray, R., Sprent, J., Weinberg, K. I., et al. (2001). IL-7 is critical for homeostatic proliferation and survival of naive T cells. Proc. Natl. Acad. Sci. U.S.A. 98, 8732-8737.
114. Tarazona, R., DelaRosa, O., Alonso, C., Ostos, B., Espejo, J., Pena, J., et al. (2000). Increased expression of NK cell markers on T lymphocytes in aging and chronic activation of the immune system reflects the accumulation of effector/senescent T cells. Mech. Ageing Dev. 121, 77-88.
115. 4+ memory T cell survival. Curr. Opin. Immunol. 23, 319-323.
116. 4+CD28null T cells in autoimmune disease: pathogenic features and decreased susceptibility to immunoregulation. J. Immunol. 179, 6514-6523.
117. Tripathi, P., Kurtulus, S., Wojciechowski, S., Sholl, A., Hoebe, K., Morris, S. C., et al. (2010). STAT5 is critical to maintain effector CD8+ T cell responses. J. Immunol. 185, 2116-2124.
118. 4+ T-cells. Mech. Ageing Dev. 131, 96-104.
119. Valenzuela, H. F., and Effros, R. B. (2002). Divergent telomerase and CD28 expression patterns in human CD4 and CD8 T cells following repeated encounters with the same antigenic stimulus. Clin. Immunol. 105, 117-125.
120. Vallejo, A. N. (2007). Immune remodeling: lessons from repertoire alterations during chronological aging and in immune-mediated disease. Trends Mol. Med. 13, 94-102.
121. 4+CD28null T cells are associated with defects in apoptotic pathways. J. Immunol. 165, 6301-6307.
122. 4+ T cells specific for Cytomegalovirus. J. Immunol. 182, 4175-4182.
123. 4+CD28- granzyme B+, Cytomegalovirus-specific T cell subset after recovery of primary Cytomegalovirus infection. J. Immunol. 173, 1834-1841.
124. Vasto, S., Colonna-Romano, G., Larbi, A., Wikby, A., Caruso, C., and Pawelec, G. (2007). Role of persistent CMV infection in configuring T cell immunity in the elderly. Immun. Ageing 4, 2.
125. Vely, F., Peyrat, M., Couedel, C., Morcet, J., Halary, F., Davodeau, F., et al. (2001). Regulation of inhibitory and activating killer-cell Ig-like receptor expression occurs in T cells after termination of TCR rearrangements. J. Immunol. 166, 2487-2494.
126. Vescovini, R., Telera, A., Fagnoni, F. F., Biasini, C., Medici, M. C., Valcavi, P., et al. (2004). Different contribution of EBV and CMV infections in very long-term carriers to age-related alterations of CD8+ T cells. Exp. Gerontol. 39, 1233-1243.
127. Walsh, N. P., Gleeson, M., Shephard, R. J., Woods, J. A., Bishop, N. C., Fleshner, M., et al. (2011). Position statement. Part one: immune function and exercise. Exerc. Immunol. Rev. 17, 6-63.
128. Wang, E., Lee, M. J., and Pandey, S. (1994). Control of fibroblast senescence and activation of programmed cell death. J. Cell. Biochem. 54, 432-439.
129. Wannamethee, S. G., Lowe, G. D., Whincup, P. H., Rumley, A., Walker, M., and Lennon, L. (2002). Physical activity and hemostatic and inflammatory variables in elderly men. Circulation 105, 1785-1790.
130. Warren, T. Y., Barry, V., Hooker, S. P., Sui, X., Church, T. S., and Blair, S. N. (2011). Sedentary behaviors increase risk of cardiovascular disease mortality in men. Med. Sci. Sports Exerc. 42, 879-885.
131. 4+ T cells: reversal by interleukin-12 stimulation. Blood 101, 3543-3549.
132. 4+ T-cell subsets in the elderly. Hum. Immunol. 68, 86-90.
133. 28- T cells in the aging immune system. Mech. Ageing Dev. 102, 131-147.
134. Wikby, A., Nilsson, B. O., Forsey, R., Thompson, J., Strindhall, J., Lofgren, S., et al. (2006). 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. Mech. Ageing Dev. 127, 695-704.
135. Xu, J., Vallejo, A. N., Jiang, Y., Weyand, C. M., and Goronzy, J. J. (2005). Distinct transcriptional control mechanisms of killer immunoglobulin-like receptors in natural killer (NK) and in T cells. J. Biol. Chem. 280, 24277-24285.
136. 4+ T cells. J. Immunol. 172, 2476-2486.
137. Yung, R., Powers, D., Johnson, K., Amento, E., Carr, D., Laing, T., et al. (1996). Mechanisms of drug-induced lupus. II. T cells overexpressing lymphocyte function-associated antigen 1 become autoreactive and cause a lupuslike disease in syngeneic mice. J. Clin. Invest. 97, 2866-2871.
138. 4+ CD28- T cell proinflammatory and effector responses in patients with coronary artery disease. J. Immunol. 181, 5233-5241.
139. Zanni, F., Vescovini, R., Biasini, C., Fagnoni, F., Zanlari, L., Telera, A., et al. (2003). Marked increase with age of type 1 cytokines within memory and effector/cytotoxic CD8+ T cells in humans: a contribution to understand the relationship between inflammation and immunosenescence. Exp. Gerontol. 38, 981-987.
140. Zlamy, M., and Prelog, M. (2009). Thymectomy in early childhood: a model for premature T cell immunosenescence? Rejuvenation Res. 12, 249-258.
141. Zoller, A. L., Schnell, F. J., and Kersh, G. J. (2007). Murine pregnancy leads to reduced proliferation of maternal thymocytes and decreased thymic emigration. Immunology 121, 207-215.