Fig 2: Engagement of PD-1 in the Subacute Phase Is Required for Durable Control of LCMV Infection(A) Plasma viral RNA load in LCMV-c13-infected B6 mice treated with anti-PD-L1 on 8–22 dpi (red dots, same as Figure 1) or 23–37 dpi (blue dots). Data are pooled from 5 experiments shown with median.(B–D) Expression of CD4, CD8, CD44, PD-1, LAG3, and LCMV-gp33-specific TCR by splenocytes (B and C) and peripheral blood mononuclear cells (D) on day 37 of LCMV-c13 infection. Representative plots are shown with median ± SD from at least 2 experiments.

Fig 3: PD-1 Blockade at the Peak of Viremia Enhances CD8 T Cell Activation with No Immediate Impact on Viral Control(A) Survival LCMV-c13-infected B6 mice following anti-PD-L1 treatment. n = 25 (control), n = 6 (days 0–8), and n = 30 (days 8–22) pooled from 3 experiments.(B) Survival of LCMV-c13-infected B6 mice after adoptive transfer of unexhausted LCMV-specific CD8 T cells and treatment with anti-PD-L1 or isotype control. Data are from 3 experiments.(C) Expression of CD4, CD8, CD44, and LCMV-gp276-specific T cell receptor (TCR) in peripheral blood mononuclear cells (PBMCs) from control and anti-PD-L1-treated mice on 14 dpi with LCMV-c13 infection. Representative plots are shown with mean ± SD from 3 experiments.(D and E) Expression of CD4, CD8, CD44, PD-1, LAG-3, and LCMV-gp33-specific TCR in PBMCs on 22 dpi. Representative plots (D) and mean ± SD from 2 experiments (E) are shown.(F) Plasma viral RNA load in LCMV-c13-infected mice on 22 dpi. Data pooled from 5 experiments are shown with median. The statistical difference was tested by the Mann-Whitney U test.See also Figure S1.

Fig 4: Maternal CD8+ T Cell-Blunted Responsiveness to Fetal Antigen Re-stimulation during Secondary Pregnancy(A) C57BL/6 (H-2b) females 21 days following allogeneic mating with Act-OVA male mice on the BALB/c background were compared to pregnant mice mid-gestation during secondary pregnancy sired by Act-OVA or non-transgenic male mice on the BALB/c background.(B) Number of H-2Kb:OVA257–264 CD8+ T cells in the spleen and pooled peripheral lymph nodes of mice described in (A).(C) Percentage of IFN-?-, TNF-a-, or IL-2-producing H-2Kb:OVA257–264 CD8+ T cells following PMA-ionomycin stimulation for each group of mice described in (A).(D) H-2Kb:OVA257_264 tetramer staining intensity and CD44 expression levels by H-2Kb:OVA257_264 CD8+ T cells for each group of mice described in (A).(E) PD-1, LAG-3, CTLA-4, and TIM-3 expression levels by H-2Kb:OVA257_264 CD8+ T cells for each group of mice described in (A).(F) Relative expression of PD-1, LAG-3, CTLA-4, and TIM-3 among H-2Kb:OVA257–264 CD8+ T cells mid-gestation during primary or secondary pregnancy, each sired by Act-OVA male mice on the BALB/c background.Data are from at least 3 independent experiments, each with similar results, with each point representing data from an individual mouse.Bar, mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.005, and ****p < 0.001.

Fig 5: The CD106+ population is uniquely localized in pancreatic injury and precancerous lesions Representative IHC staining of tumor core and adjacent region in PDAC patient (stage II) for CD106+. The corresponding magnification insets of the tumor core (red dotted line) or adjacent region (green dotted line) are displayed on the right. Scale bar, 500 µm in gross, 20 µm in magnification.Immunofluorescence staining of the pancreas obtained from a 2.5-month-old KC mouse for CD106 (red), a-SMA (green) or CK19 (green), and DAPI (blue). Scale bar, 50 µm, 10 µm.Gating strategy for the identification of the CD106+CD24+CD44+ population in KC and WT mice. FACS analysis of the percentage of CD106+ among CD45-CD31- cells; each dot represents one mouse. The bars are representing the mean. The P-values were calculated using Student's t-test.Immunofluorescence staining of pancreases obtained from a KC mouse (left) and a 2.5-month-old KPC mouse (right) for CD44 (green), CD24 (red), and DAPI (blue). Scale bar, 50, 10 µm. Source data are available online for this figure.