Extended Data Fig. 4: Ammonia promotes T cell apoptosis and inhibits T cell proliferation.
From: The malate shuttle detoxifies ammonia in exhausted T cells by producing 2-ketoglutarate
a–d, Got1-deficient and -sufficient donor P14 CD8+ T cells were isolated from C57BL/6 host mice infected with LCMV Armstrong 8 days earlier. A total of 0.25 × 106 cells were cultured with anti-CD3 and anti-CD28 in the presence or absence of NH4OH for 2 days. FACS plots (a–b) and line graphs (c–d) show the percentages of AnnexinV+ PI+ cells (a, c) and Ki-67+ cells (b, d). Data are combined from two experiments with three mice in total. The results are presented as mean ± s.d. *P<0.05; **P<0.01; ***P<0.001; ****P<0.0001. Comparisons were performed using two-way ANOVA. P values in c (from left to right): 3.6 × 10−6, 0.026, 0.0006, 0.003, 5.3 × 10−6, 9.7 × 10−9; in d: 0.0006, 2.3 × 10−7, 1.9 × 10−11, 6.3 × 10−7, 4.0 × 10−5, 4.8 × 10−7. Six-week-old female mice were used (a–d).
