Daan Pieren

25 General introduction and scope of this thesis 72. Saligrama, N. et al. Opposing T cell responses in experimental autoimmune encephalomyelitis . Nature 572, 481-487, doi:10.1038/s41586-019-1467-x (2019). 73. Suzuki, M. et al. CD8+CD45RA+CCR7+FOXP3+ T cells with immunosuppressive properties: a novel subset of inducible human regulatory T cells . J. Immunol. 189, 2118- 2130, doi:10.4049/jimmunol.1200122 (2012). 74. Brien, J. D. et al. Key role of T cell defects in age-related vulnerability to West Nile virus . J. Exp. Med. 206, 2735-2745, doi:10.1084/jem.20090222 (2009). 75. Smithey, M. J. et al. Increased apoptosis, curtailed expansion and incomplete differentiation of CD8+ T cells combine to decrease clearance of L. monocytogenes in old mice . Eur. J. Immunol. 41, 1352-1364, doi:10.1002/eji.201041141 (2011). 76. Po, J. L. et al. Age-associated decrease in virus-specific CD8+ T lymphocytes during primary influenza infection . Mech. Ageing Dev. 123, 1167-1181, doi:10.1016/s0047- 6374(02)00010-6 (2002). 77. Effros, R. B. et al. Diminished T-cell response to influenza virus in aged mice . Immunology 49, 387-392 (1983). 78. Yager, E. J. et al. Age-associated decline in T cell repertoire diversity leads to holes in the repertoire and impaired immunity to influenza virus . J. Exp. Med. 205, 711-723, doi:10.1084/ jem.20071140 (2008). 79. Decman, V. et al. Cell-intrinsic defects in the proliferative response of antiviral memory CD8 T cells in aged mice upon secondary infection . J. Immunol. 184, 5151-5159, doi:10.4049/jimmunol.0902063 (2010). 80. Zhou, X. et al. Age-related changes in memory and effector T cells responding to influenza A/H3N2 and pandemic A/H1N1 strains in humans . Vaccine 29, 2169-2177, doi:10.1016/j. vaccine.2010.12.029 (2011). 81. Deng, Y. et al. 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, doi:10.4049/ jimmunol.172.6.3437 (2004). 82. Briceno, O. et al. Reduced naive CD8(+) T-cell priming efficacy in elderly adults . Aging Cell 15, 14-21, doi:10.1111/acel.12384 (2016). 83. Lopez-Otin, C. et al. The hallmarks of aging . Cell 153, 1194-1217, doi:10.1016/j.cell.2013.05.039 (2013). 84. Xue, W. et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas . Nature 445, 656-660, doi:10.1038/nature05529 (2007). 85. Wherry, E. J. et al. Molecular and cellular insights into T cell exhaustion . Nat. Rev. Immunol. 15, 486-499, doi:10.1038/nri3862 (2015). 86. Scudellari, M. To stay young, kill zombie cells . Nature 550, 448-450, doi:10.1038/550448a (2017). 87. Rodier, F. et al. Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion . Nat. Cell Biol. 11, 973-979, doi:10.1038/ncb1909 (2009). 88. Appay, V. et al. Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections . Nat. Med. 8, 379-385, doi:10.1038/nm0402-379 (2002). 89. Akbar, A. N. et al. Are senescence and exhaustion intertwined or unrelated processes that compromise immunity? Nat. Rev. Immunol. 11, 289-295, doi:10.1038/nri2959 (2011). 90. Henson, S. M. et al. Reversal of functional defects in highly differentiated young and old CD8 T cells by PDL blockade . Immunology 135, 355-363, doi:10.1111/j.1365- 2567.2011.03550.x (2012). 91. Plunkett, F. J. et al. The loss of telomerase activity in highly differentiated CD8+CD28- CD27- T cells is associated with decreased Akt (Ser473) phosphorylation . J. Immunol. 178, 7710-7719, doi:10.4049/jimmunol.178.12.7710 (2007). 92. Lanna, A. et al. The kinase p38 activated by the metabolic regulator AMPK and scaffold TAB1 drives the senescence of human T cells . Nat. Immunol. 15, 965-972, doi:10.1038/ ni.2981 (2014). 93. Lanna, A. et al. A sestrin-dependent Erk-Jnk-p38 MAPK activation complex inhibits immunity during aging . Nat. Immunol. 18, 354-363, doi:10.1038/ni.3665 (2017). 94. Liu, Y. et al. Expression of p16(INK4a) in peripheral blood T-cells is a biomarker of human aging . Aging Cell 8, 439-448, doi:10.1111/j.1474-9726.2009.00489.x (2009). 1