The PD-1/PD-L1 Pathway Affects the Expansion and Function of Cytotoxic CD8(+) T Cells During an Acute Retroviral Infection

David, Paul; Megger, Dominik A.; Kaiser, Tamara; Werner, Tanja; Liu, Jia; Chen, Lieping; Sitek, Barbara; Dittmer, Ulf; Zelinskyy, Gennadiy

Activated effector CD8 + T cells eliminate FV-infected cells during acute infection. Since PD-1 and especially PD-L1 deficiency influenced the frequencies of virus-specific effector CD8 + T cells during acute FV infection, we analyzed if this had an effect of the viral load kinetics. The replication of FV was reduced in the spleens of PD-1 −/− ( Figure 1E ) and in the BM (Figure 1F ) of PD-L1 −/− mice before CD8 + T cells expanded, suggesting that these effects might not be associated with effector T cell responses. However, at day 8 after infection, as well as day 10 in the spleen, viral loads were significantly higher in WT mice compared to animals deficient for PD-1 or PD-L1, which might reflect differences in CD8 + T cell responses. At later time points no differences in viral loads were observed between the mouse strains, with the exception of a low viral load in PD-1 KO mice at day 12 in the BM ( Figure 1F) . Thus, the reduction in viral loads in both KO mice at day 8 and 10 after FV infection may be a result of an accelerated expansion of effector CD8 + T cells in mice without PD-1 signaling.