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

Our current data show that both PD-1 receptor deficiency as well as PD-1 ligand deficiency influences CD8 + T cell responses during an acute viral infection. Interestingly, the effect of PD-L1 knockout was stronger in almost all measurements than the effect of PD-1 knockout, which raised the question what is the difference between the two mouse models. It was previously shown that CD80 expressed on activated T cells may function as additional receptor of PD-L1 and delivers suppressive signals to T cells (36) . In order to determine the role of CD80 as additional inhibitory receptor, we analyzed the expression of CD80 on effector and virus-specific CD8 + T cells after FV infection. Approximately 34% of the effector CD8 + CD43 + T cells and 38% of the virus-specific CD8 + tetramer + CD8 + T cells in the spleens of 10 day infected WT mice expressed CD80 on the cell surface (Figures 6A,B) . So there might be a possible role of CD80 in suppressing CD8 + T cell responses. However, the treatment of FV-infected WT or PD-1 −/− mice with the blocking anti-CD80 antibody (37) did not affect the numbers of effector CD43 + CD8 + T cells or virus-specific CD8 + tetramer + T cells in the spleen or BM of FV-infected mice (Figures 6C,D) . The production of GzmB by CD8 + T cells and FV viral loads were also not changed after blocking CD80 (data not shown). Thus, the CD80 expression on FV-induced effector CD8 + T cells was not involved in the PD-L1 dependent regulation of this population.