Figure 2. PD-L2 protects against lethal malaria and has translational potential.

The expression of PD-L2 on dendritic cells determines effector T cell function following a PD-1/PD-L1 interaction. During non-lethal malaria (top right), DCs express PD-L2 which inhibits the immunosuppressive PD-1/PD-L1 interaction while interacting with an unknown receptor (?) to improve T cell functions. This leads to protective immunity characterised by increased T-box transcription factor TBX21 (Tbet) expression, increase interferon-γ (IFN-γ) secretion and better proliferation in response to the parasite. In contrast, during lethal malaria (left), PD-L2 expression is low or absent and this allows the immunosuppressive PD-1/PD-L1 interaction to generate exhausted T cells which do not express Tbet, do not secrete IFN-γ and cannot proliferate in response to the parasite. Soluble PD-L2 administered to mice infected with lethal malaria (lower right) can prevent T cell exhaustion.