Fig 2: Attenuated CAF-induced antigen-mediated AICD effects of CD8+ T cells by Cal/ICG@MPs.a Scheme of attenuated myofibroblast-induced antigen-mediated AICD effect of CD8+ T cells by Cal/ICG@MPs. The cell supernatants were collected after tumor cells were treated with PBS, ICG, Cal/ICG, ICG@MPs, Cal@MPs, or Cal/ICG@MPs at the ICG concentration of 4 µg mL-1 and Cal concentration of 60 ng mL-1 for 4 h in the presence or absence of 808 nm laser irradiation (1 W cm-2, 5 min). Myofibroblasts were pretreated with PBS, ICG, Cal/ICG, ICG@MPs, Cal@MPs, or Cal/ICG@MPs at the ICG concentration of 4 µg mL-1 and Cal concentration of 60 ng mL-1 for 48 h, and then co-cultured with the above tumor cell supernatants for 24 h. Finally, the treated myofibroblasts were co-cultured with CD8+ T cells for another 48 h. The phenotype of myofibroblasts and CD8+ T cells was analyzed by flow cytometry. b MHC-I MFI in myofibroblasts after the pretreated myofibroblasts were co-cultured with the cell supernatants from the treated H22 cells indicated in a. Data are presented as means ± s.d. (n = 3 biologically independent samples; one-way ANOVA followed by Tukey’s HSD post hoc test). c, d FasL (c) and PD-L2 (d) expression in myofibroblasts after the pretreated myofibroblasts were co-cultured with the cell supernatants from the treated H22 cells, and then CD8+ T cells indicated in a. Data are presented as means ± s.d. (n = 3 biologically independent samples; one-way ANOVA followed by Tukey’s HSD post hoc test). e, f Proliferation (e) and apoptosis (f) ratios of CD8+ T cells after treatment are indicated in a. Data are presented as means ± s.d. (n = 3 biologically independent samples; one-way ANOVA followed by Tukey’s HSD post hoc test). g–i MHC-I (g), FasL (h), and PD-L2 (i) expression in CAFs of stroma-rich H22 tumor-bearing mice at 14 days after intravenous injection of PBS, ICG, Cal/ICG, ICG@MPs, Cal@MPs, or Cal/ICG@MPs at the ICG dosage of 8 mg kg-1 and Cal dosage of 120 µg kg-1 twice every 2 days, followed with or without 808 nm laser irradiation (1.5 W cm-2, 10 min) at 2 h after the last injection by flow cytometry. Data are presented as means ± s.d. (n = 6 mice per group; one-way ANOVA followed by Tukey’s HSD post hoc test). j, k The numbers (j) and ratios (k) of CD8+ T cells in tumor tissues of stroma-rich H22 tumor-bearing mice after treatment are indicated in g. Data are presented as means ± s.d. (n = 6 mice per group; one-way ANOVA followed by Tukey’s HSD post hoc test). Source data are provided as a Source Data file.

Fig 3: IL-18-Induced Fasl Exacerbates Liver Inflammation(A) Single-cell RNA sequencing was performed on Il17rafl/fl and Il17rafl/fl × villin cre+ liver cells enriched for mononuclear cells 90 min post Con A (25 mg/kg) (n = 2 mice/group). t-SNE plots of Fasl+ cells colored according to relative expression level and reference t-SNE of cell types.(B–D) Flow cytometry analysis of liver FasL+ cells of naive littermate Il17rafl/fl and Il17rafl/fl × villin cre+ mice (n = 7–11 mice/group). (B) Number of live FasL+ cells plotted as fold changeover of Il17rafl/fl. (C) FasL geometric mean fluorescence intensity (gMFI) of live FasL+ cells. (D) Representative histogram of FasL+ cells.(E–G) Wild-type controls and Il17rafl/fl × villin cre+ mice (n = 6–28 mice/group) were treated with i.v. anti-FasL (250–500 µg/mouse) 1 h prior to i.v. Concanavalin A (25 mg/kg). Serum alanine aminotransferase (ALT) (E) and TUNEL staining (F) was analyzed 8 h post Con A. (G) Representative images of TUNEL-stained liver.(H and I) Liver mononuclear cells from naive littermate Il17rafl/fl and Il17rafl/fl × villin cre+ mice were stimulated ex vivo with 50 ng/mL IL-18 ± 5 µg/mL anti-IFN? (aIFN?) and analyzed by flow cytometry. Percent (H) and actual number (I) of TCRß+FasL+ cells (gated on live CD90+ cells). Lines connect paired samples. Each dot/line represents one mouse.(B, C, E, and F) Data are represented as mean + SEM.(unpaired t test, one-way ANOVA with multiple comparisons test, two-way ANOVA with multiple comparisons test). p<0.05*, <0.01**, <0.001***, <0.0001****

Fig 4: 6PGD-/- CD8+ T cells display a TEFF phenotype(A) CD8+ T cells were isolated from spleen of 6PGD-/- and 6PGDfl/fl mice and stimulated for 48 h with aCD3 + aCD28 mAbs, followed by RNA extraction and RNA-sequencing analysis. Heatmap of gene expression for 6PGD-/- versus 6PGDfl/fl CD8+ T cells is shown.(B) For confirmation, naive (CD62Lhigh CD44low) CD8+ T cells were isolated and stimulated for 4 days with aCD3 + aCD28 mAbs and IL-2 (20 IU/mL). Expression of representative genes was confirmed by real-time PCR on day 0 and day 4.(C–M) Naive CD8+ T cells were stimulated for 4 days with aCD3 + aCD28 mAbs and IL-2 (20 IU/mL) followed by assessment of IFN-? expression by intracellular staining (C) and quantification of IFN-? production by ELISA (D). Expression of granzyme B (E–F), T-bet (G and H), Fas (CD98) (I and J), FasL (CD178) (K and L), and CD69 (M) was assessed by flow cytometry. Results are representative of three independent experiments with n = 6 mice per group. Error bars represent ± SEM. ***p < 0.001; ****p < 0.0001.

Fig 5: iNKT Cells Induce IL-1ß Secretion by BMDCs during Infection with Microbes that Fail to Elicit Strong IL-1ß Release in a Cell-Intrinsic MannerBMDCs were infected with (A) B. fragilis or (B) C. trachomatis at increasing MOIs, washed, and cultured alone or with iNKT cells for 24 h in the presence of a FasL-blocking antibody (aFasL mAb) or an isotype control. IL-1ß release was quantified by ELISA. Error bars represent mean + SD of triplicate samples; panels are representative of three and two independent experiments, respectively.