Figure 6. Immune cells recognize senescent cells.

A. Immune cells are adjacent to activated HSCs in vivo as identified by electron microscopy of normal and fibrotic mouse livers. Immune cells (lp – lymphocytes, mφ-macrophage, np – neutrophil) localize adjacent to activated HSC. Scale bar is 5μm. B. Immune cells identified by CD45R (CD45) reside in close proximity to senescent cells (identified by p21, p53 and Hmga1) in mouse fibrotic liver. C, D. Senescent can be recognized by immune cells in vitro. Images from time lapse microscopy of the same field at start (0) and 10 hours after presenting interaction between NK cells (uncolored) and growing (C) or senescent (D) IMR-90 (pseudocolored, green) cells. Original images and time points are presented in Supplementary Figure 4. Scale bar is 100μm. E, F. Human NK cell line, YT, exhibits preferential cytotoxicity in vitro towards senescent activated HSCs (E) or senescent IMR-90 cells (F) compared to growing cells. In IMR-90 cells senescence was induced by DNA damage, extensive passaging in culture or by infection with oncogenic ras^V12. Both uninfected and empty vector infected growing cells were used as controls. At least three independent experiments were performed in duplicates. Cytotoxicity based on crystal violet quantification at OD595 are shown, **-p<0.005 using Student’s t-test.