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

The kinetic of effector CD8 + T cells specific for the FV gagL epitope was very similar to the kinetic of the total effector CD8 + CD43 + population. The first virus-specific cells were detectable in the spleens of WT mice at day 7 after infection ( Figure 1C) . In both KO mouse strains the numbers of virus-specific CD8 + tetramer + T cells were higher at this time point than in WT mice. Peak expansion of virus-specific CD8 + T cells was at day 10 in both organs and again frequencies were enhanced in KO mice in comparison to WT mice. In PD-L1 −/− mice the number of virusspecific CD8 + T cells was more than 3.5 times higher than in WT mice at this time point (Figure 1D ). In the group with PD-1 deficiency, cell numbers of virus-specific CD8 + T cells were only moderately enhanced in comparison to WT mice, whereas the population of virus-specific CD8 + T cells was largely expanded in the group of mice with PD-L1 deficiency on day 10, 12, and 15 after infection in the spleen and BM (Figures 1C,D) . Again, a T cell contraction phase was not detected in the spleen of PD-L1 −/− mice until 15 dpi. Thus, especially the deficiency for the PD-1 ligand resulted in a less controlled expansion of effector CD8 + T cells during an acute retroviral infection.