Experimental evidence suggests that insufficient signaling through the PD-1 pathway promotes immunopathology during acute infection by exaggerating primary T cell responses.
The upregulation of immune checkpoint molecules, such as programmed cell death protein 1 (PD1) and cytotoxic T lymphocyte antigen 4 (CTLA4), on immune cells occurs during acute infections, such as malaria, as well as during chronic persistent viral infections, including HIV and hepatitis B virus.