Daan Pieren

180 Chapter 6 Figure 5. Targeting age-related T-cell exhaustion and senescence should aim to achieve balance. Schematic representation of the balance between fully competent T cells and exhausted or senescent T cells, which may be regarded as immunoregulatory cells. As indicated, a high amount of exhausted T cells commonly observed with aging dampens the host’s response to infectious diseases and limits killing of tumor cells, although pathogen-induced immune pathology and autoimmune responses caused by fully functional T cells is limited. In contrast, a low number of exhausted T cells may provide superior killing of virally infected cells and tumor cells, but at the risk of increased immune pathology and breaking tolerance. Interventions targeting exhausted or senescent T cells should aim to stabilize this balance, providing optimal protection against infectious diseases and tumors, whilst limiting immune pathology and autoimmune disease. FUTURE PERSPECTIVES In this thesis, we provide new insights into the impact of aging on T cells in mice and humans. As we show the importance of studying the change of T-cell response kinetics with age, it would be of great significance to address the in vivo impact of delayed T-cell activation and impaired T-cell proliferation on the response to vaccination or infection. It has indeed been speculated that minor changes in these tightly regulated processes may have a great negative impact on T-cell mediated protection [98]. Thus, assessing the role of slower and lower