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 virus-specific effector CD8 + T cells use the cytotoxic degranulation pathway for the elimination of FV-infected cells (30) . In the next experimental step we analyzed the numbers of effector CD8 + T cells and virus-specific Tetramer + CD8 + T cells producing the cytotoxic serine protease granzyme B (GzmB) in spleen and BM of infected WT, PD-1 −/− , and PD-L1 −/− mice. The frequency of GzmB + effector CD8 + CD43 + T cells was enhanced at day 7 after infection in spleens (Figure 2A ) and in BM ( Figure 2B ) of PD-1 −/− and PD-L1 −/− mice in comparison to WT mice. Between day 8 and 10 post infection the numbers of effector CD8 + T cells producing GzmB were significantly higher in both KO mouse strains than in WT mice. Later, at day 12 and day 15 after infection, the numbers of effector cells producing GzmB in the spleen were reduced and were similar to the numbers of GzmB producing cells in WT mice. However, in BM the numbers of CD8 + CD43 + GzmB + cells remained enhanced in both KO mouse strains at most of the later time points after infection ( Figure 2B) .