Daan Pieren

169 General discussion and future perspectives Figure 2. The redefined human virtual memory cell subset: KIR + RA + T cells and NKG2A + RA + T cells. ( A ) Schematic representation of the CD8 + T-cell population in young individuals and aged individuals, indicating accumulation of suppressive KIR + RA + T cells (CD45RA + KIR + NKG2A - ) and the decline of NKG2A + RA + T cells (CD45RA + KIR - NKG2A + ) with age. ( B ) Based on our combined RNA sequencing, flow cytometric analyses, and stimulation assays, we present KIR + RA + T cells and NKG2A + RA + T cells as two phenotypically distinct subsets. We found KIR + RA + T cells to express markers related to regulation (TIGIT, Helios, CD122, FCRL3), killing (CD107a, Granzyme H, NCR1), and exhaustion (TOX, KLRG1), whereas NKG2A + RA + T cells express markers related to co-stimulation (CD28, CD226), and co-inhibition (CTLA-4, TIM-3). 6