Prion protein modulation of virus-specific T cell differentiation and function during acute viral infection

Figure 1.. Prnp deletion results in increased virus-specific memory CD8+ T cells. WT and Prnp–/– mice were infected with LCMV Armstrong and spleens were harvested at indicated time points. (A) Frequencies of tetramer+ CD8+ T cells at 8 dpi and representative FACS plots. (B) Numbers of tetramer+ CD8+ T cells at 8 dpi. (C) Frequencies of tetramer+ CD8+ T cells at 27 dpi and representative FACS plots. (D) Numbers of tetramer+ CD8+ T cells at 27 dpi. *P < 0.05.

Figure 2.. Prnp deletion does not change PD-1 and CD127 expression levels in virus-specific CD8+ T cells. WT and Prnp–/– mice were infected with LCMV Armstrong and spleens were harvested at indicated time points. (A) Mean fluorescence intensity (MFI) of PD-1 in tetramer+ CD8+ T cells at 8 dpi. (B) MFI of CD127 in tetramer+ CD8+ T cells at 8 dpi. (C) MFI of CD127 in tetramer+ CD8+ T cells at 27 dpi.

Figure 3.. Prnp deletion results in decreased proliferation of virus-specific memory CD8+ T cells. WT and Prnp–/– mice were infected with LCMV Armstrong and spleens were harvested at indicated time points. (A) Frequencies of Ki67+ in tetramer+ CD8+ T cells at 8 dpi. (B) Frequencies and FACS plot representative of Ki67+ in tetramer+ CD8+ T cells at 27 dpi. *P < 0.05, **P < 0.001.

Figure 4.. Prnp deletion alters virus-specific memory CD8+ T cell subset differentiation. WT and Prnp–/– mice were infected with LCMV Armstrong and spleens were harvested at 27 dpi. Frequencies and representative FACS plots of Tcm cells (CD127+, CD62L+), (Tem cells (CD127+, CD62L–), and Ttem cells (CD127–, CD62L–) in (A) GP33–41 tetramer+ and (B) GP394–404 tetramer+ CD8+ T cells. Numbers of Tcm cells (CD127+, CD62L+), Tem cells (CD127+, CD62L–), and Ttem cells (CD127–, CD62L–) in (C) GP33–41 tetramer+ and (D) GP394–404 tetramer+ CD8+ T cells. (E) The ratio of Tem cells to Ttem cells is shown for each tetramer. *P < 0.05, **P < 0.001, ***P < 0.005, and ****P < 0.0001.

Figure 5.. Prnp deletion does not change the effector function of virus-specific effector CD8+ T cells early postinfection. Spleens were isolated from WT and Prnp–/– LCMV Armstrong–infected mice at 8 dpi and stimulated ex vivo with indicated LCMV peptides. Frequencies and representative FACS plots of IFNγ+ and IFNγ+TNFα+ in (A) GP33–41 peptide–stimulated and (B) NP396–404 peptide–stimulated CD8+ T cells. *P < 0.05.

Figure 6.. Prnp deletion increases the numbers of cytokine-producing virus-specific memory CD8+ T cells. Spleens were isolated from WT and Prnp–/– LCMV Armstrong–infected mice at 27 dpi and stimulated ex vivo with indicated LCMV peptides. Frequencies and representative FACS plots of IFNγ+ and IFNγ+TNFα+ in (A) GP33–41 peptide–stimulated and (B) NP396–404 peptide–stimulated CD8+ T cells. Numbers of IFNγ+ and IFNγ+TNFα+ in (C) GP33–41 peptide–stimulated and (D) NP396–404 peptide–stimulated CD8+ T cells. (E) The frequencies of IFNγ+CD107+ CD8+ T cells stimulated with GP33–41 and NP396–404 peptides and representative FACS plots. *P < 0.05, **P < 0.001.

Figure 7.. Prnp deletion results in increased numbers of virus-specific CD4+ memory T cells. Spleens were isolated from WT and Prnp–/– LCMV Armstrong–infected mice at and 8 and 27 dpi, and the immune response was characterized. (A) Frequencies and numbers of tetramer+ CD4+ T cells at 8 dpi. (B) Frequencies and representative FACS plots of IFNγ+ and IFNγ+TNFα+ in GP66–76 peptide–stimulated ex vivo CD4+ T cells at 8 dpi. (C) Frequencies and FACS plot representatives of IFNγ+ and IFNγ+TNFα+ in GP66–76 peptide–stimulated ex vivo CD4+ T cells at 27 dpi. (D) Numbers of IFNγ+ and IFNγ+TNFα+ in GP66–76 peptide–stimulated ex vivo CD4+ T cells at 27 dpi. *P < 0.05.