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 current study used the PD-1 −/− and PD-L1 −/− mouse strains for a kinetic analysis of CD8 + T cell responses and FV load. We observed an enhanced expansion of CD8 + effector T cells in both KO mouse strains during the early acute phase of FV infection (Figure 1) . PD-L1/PD-1 signaling regulated the proliferation, functional maturation, and apoptosis of virusspecific CD8 + T cells. However, CD80 was not involved in the PD-L1-mediated suppression of CD8 + T cell responses. In previous studies it was shown that deficiency in the PD-1/PD-L1 pathway or the blockade of the interaction between these molecules resulted in an enhanced elimination of the adenovirus (38), LP-BM5 immunodeficiency retrovirus (39), human metapneumovirus (HMPV) induced acute respiratory infections (40) , rabies virus (41), LCMV (23) , and FV (13). On the other hand the absence of PD-1 suppression during acute corona virus infection (42) , murine hepatitis virus strain-3 (MHV-3) (43) or LCMV infection (44, 45) lead to an enhanced immunopathology and mortality of infected animals. In the case of FV infection, the main target organs of FV replication are BM and spleen. Short-term inflammation or immunopathology in these organs are usually not life-threatening for infected animals.