Daan Pieren

26 Chapter 1 95. Henson, S. M. et al. KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells . Blood 113, 6619-6628, doi:10.1182/blood-2009-01-199588 (2009). 96. Di Mitri, D. et al. Reversible senescence in human CD4+CD45RA+CD27- memory T cells . J. Immunol. 187, 2093-2100, doi:10.4049/jimmunol.1100978 (2011). 97. Moskophidis, D. et al. Virus persistence in acutely infected immunocompetent mice by exhaustion of antiviral cytotoxic effector T cells . Nature 362, 758-761, doi:10.1038/362758a0 (1993). 98. Wherry, E. J. T cell exhaustion . Nat. Immunol. 12, 492-499 (2011). 99. Wherry, E. J. et al. Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment . J. Virol. 77, 4911-4927, doi:10.1128/jvi.77.8.4911-4927.2003 (2003). 100. Freeman, G. J. et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation . J. Exp. Med. 192, 1027-1034, doi:10.1084/jem.192.7.1027 (2000). 101. Barber, D. L. et al. Restoring function in exhausted CD8 T cells during chronic viral infection . Nature 439, 682-687, doi:10.1038/nature04444 (2006). 102. Lages, C. S. et al. Partial restoration of T-cell function in aged mice by in vitro blockade of the PD-1/ PD-L1 pathway . Aging Cell 9, 785-798, doi:10.1111/j.1474-9726.2010.00611.x (2010). 103. Channappanavar, R. et al. Advancing age leads to predominance of inhibitory receptor expressing CD4 T cells . Mech. Ageing Dev. 130, 709-712, doi:10.1016/j.mad.2009.08.006 (2009). 104. Shimada, Y. et al. Age-associated up-regulation of a negative co-stimulatory receptor PD-1 in mouse CD4+ T cells . Exp. Gerontol. 44, 517-522, doi:10.1016/j.exger.2009.05.003 (2009). 105. Shimatani, K. et al. PD-1+ memory phenotype CD4+ T cells expressing C/EBPalpha underlie T cell immunodepression in senescence and leukemia . Proc. Natl. Acad. Sci. U. S. A. 106, 15807-15812, doi:10.1073/pnas.0908805106 (2009). 106. Lee, K. A. et al. Characterization of age-associated exhausted CD8(+) T cells defined by increased expression of Tim-3 and PD-1 . Aging Cell 15, 291-300, doi:10.1111/acel.12435 (2016). 107. Decman, V. et al. Defective CD8 T cell responses in aged mice are due to quantitative and qualitative changes in virus-specific precursors . J. Immunol. 188, 1933-1941, doi:10.4049/ jimmunol.1101098 (2012). 108. Song, Y. et al. T-cell Immunoglobulin and ITIM Domain Contributes to CD8(+) T-cell Immunosenescence . Aging Cell 17, doi:10.1111/acel.12716 (2018). 109. Johnston, R. J. et al. The immunoreceptor TIGIT regulates antitumor and antiviral CD8(+) T cell effector function . Cancer Cell 26, 923-937, doi:10.1016/j.ccell.2014.10.018 (2014). 110. Chew, G. M. et al. TIGIT Marks Exhausted T Cells, Correlates with Disease Progression, and Serves as a Target for Immune Restoration in HIV and SIV Infection . PLoS Pathog. 12, e1005349, doi:10.1371/journal.ppat.1005349 (2016). 111. Kong, Y. et al. T-Cell Immunoglobulin and ITIM Domain (TIGIT) Associates with CD8+ T-Cell Exhaustion and Poor Clinical Outcome in AML Patients . Clin. Cancer Res. 22, 3057- 3066, doi:10.1158/1078-0432.CCR-15-2626 (2016). 112. Pauken, K. E. et al. TIGIT and CD226: tipping the balance between costimulatory and coinhibitory molecules to augment the cancer immunotherapy toolkit . Cancer Cell 26, 785-787, doi:10.1016/j.ccell.2014.11.016 (2014). 113. Yu, X. et al. The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells . Nat. Immunol. 10, 48-57, doi:10.1038/ni.1674 (2009). 114. Zheng, H. Y. et al. Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients . Cell. Mol. Immunol., doi:10.1038/s41423-020-0401-3 (2020). 115. Ferrucci, L. et al. Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty . Nat. Rev. Cardiol. 15, 505-522, doi:10.1038/s41569-018-0064-2 (2018).