Daan Pieren

167 General discussion and future perspectives Figure 1. Potential mechanism of regulatory T-cell accumulation with age. Schematic representation of the hypothesized causes for the accumulation of Tregs with age. At young age, tissue cells are fully functional and homogeneous. The balance between the proportions of Treg and helper T cells (Th cells) is shifted to Th cells. During aging, tissue cells increasingly develop into senescent cells that secrete the pro-inflammatory senescence- associated phenotype (SASP), including high levels of IL-6. Presence of pro-inflammatory IL-6 promotes the accumulation of Tregs, leading to a shift in balance to Tregs. Insight into this process is highlighted by the Ercc1 -/ Δ 7 mouse model, which is a model for compromised DNA-repair induced senescent cells, increased levels of IL-6, and accumulation of Tregs. VIRTUAL MEMORY T CELLS: A SUBSET COMPRISING TWO DIFFERENT CELL TYPES Virtual Memory T cells In addition to ongoing research on more established T-cell subsets, novel T-cell subsets are still being discovered. A recently described CD8 + T-cell subset are ‘virtual memory T cells’. Virtual memory cells were initially identified in wildtype and germ-free mice, and were described as CD8 + T cells that express memory phenotype and functionality without having encountered cognate antigen [36]. This led to the hypothesis that virtual memory cells arise via homeostatic proliferation in response to cytokines derived from other cells in their microenvironment. Virtual memory cells have been shown to control Listeria monocytogenes infection in mice [37] in an IL-15-dependent manner acting 6