Extended Data Fig. 10: Auto-aggressive human CD8 T cells.
From: Auto-aggressive CXCR6+ CD8 T cells cause liver immune pathology in NASH
a, Auto-aggression of allogeneic and autologous CD8 T cells against primary human hepatocytes after incubation with IL-15 (effector-to-target ratio of 3:1 (n = 3)). b, Auto-aggression by IL-15-treated human CD8 T cells exposed to acetate (n = 3). c, Acetate levels in livers from unaffected individuals or patients with NASH (n = 3). d, Auto-aggression of human CD8 T cells in presence of anti-TNF (10 μg ml−1) or anti-LFA1 (10 μg ml−1) (n = 3). e, f, Auto-aggression against MHC-I-deficient K562 cells by human CD8 T cells exposed to IL-15 (e), and at different effector-to-target ratios (n = 6). g, Calcium influx in IL-15-treated human CXCR6+CD69+ CD8 T cells measured with a calcium sensor dye before or after coculture with K562 cells and quantification (n = 6). h, i, Auto-aggressive killing of K562 cells by IL-15-treated CD8 T cells in presence of anti-FasL (10 μg ml−1), anti-NKG2D (10 μg ml−1) or EGTA (4 mM) at effector-to-target ratio of 10:1 (n = 6). j, Mean numbers of CD8 T cells adjacent to cleaved CASP3+ hepatocytes in mice fed a normal diet and NASH mice (n = 3). k, l, Surface FasL and TRAIL expression of mouse CXCR6+ CD8 T cells after 1 h exposure to ATP (200 μM). m, Caspase activity in primary mouse hepatocytes cocultured with auto-aggressive CD8 T cells and anti-FasL (10 μg ml−1) (n = 3). n, Mouse CD8 T cell auto-aggression in presence of inhibitors against apoptosis (zVAD-FMK, 10 μM) or necroptosis (Nec-1s, 30 μM) (n = 4). o, sALT at day 2 after adoptive transfer of IL-15-treated, acetate-exposed CD8 T cells and anti-FasL injection (100 μg per mouse). Two independent experiments. Exact P (a–o) and n (k, l, o) values are presented in Source Data. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Two-way ANOVA with Sidak’s (a) and Tukey’s (f, g) multiple comparison test, one-way ANOVA with Tukey’s multiple comparison test (b, d, e, h, i, m–o) and unpaired two-tailed t-test (c, j–l). In a–o, data are mean ± s.e.m., error is reported as s.d.
