Programmed death-1 ligand (PD-L1) is emerging as a player in the complex disease known as multiple sclerosis. Multiple sclerosis, characterized by chronic inflammatory demyelination in the central nervous system, is an autoimmune disease mediated by autoreactive activated T cells. Th1-type inflammatory T cells express the receptor for PD-L1, and when the receptor is blocked from binding with PD-L1, T cells become inhibited. Therefore, as previous studies have shown, PD-L1 is important in inhibiting Th1-type autoimmune diseases, and PD-L1 knockout mice with induced autoimmune diseases show aggravated symptoms. A group from Soochow University in China recently published in Neural Regeneration Research their research on PD-L1 involvement in experimental allergic encephalomyelitis, a mouse model that closely mimics multiple sclerosis in humans.
This study had a number of highlights. Uniquely, the group induced allergic encephalomyelitis in mice using a single subcutaneous injection of myelin oligodendrocyte glycoprotein, complete Freund’s adjuvant, and Bordetella pertussis into the armpit, allowing easy transport of the antigen and avoiding the chance of antigen sensitization. Mice developed allergic encephalomyelitis that was similar to multiple sclerosis, as identified by hematoxylin-eosin staining, Luxol fast-blue staining, and neurological function scores. Mice injected with phosphate buffered saline served as controls and did not develop signs of allergic encephalomyelitis.
Immunohistochemical staining of the spinal cords of experimental mice showed significant infiltration of inflammatory cells around blood vessels, and they were expressing PD-L1. Control mice showed no such infiltration or PD-L1 immunoreactivity. Specifically, by way of flow cytometry, the researchers found PD-L1 expression of splenic CD4+ T cells was significantly increased compared to the control group two days after the onset of allergic encephalomyelitis. Protein samples taken from the CD4+ T cells confirmed this finding.
It is not surprising that PD-L1 is involved in multiple sclerosis, as it is expressed by immune-privileged organs such as brain, placenta, and cornea. The researchers wrote that “[PD-L1] might down-regulate the immune response of autoreactive T and B cells in peripheral tissues, thereby maintaining immune tolerance of peripheral organs, a mechanism associated with the inhibition of T cells-mediated immune damage to peripheral organs.” It was suggested that PD-L1 be studied further to evaluate its contribution to multiple sclerosis development, remission, relapse, and treatment.