Abstract
Purpose :
CD8+ T cells play a critical role in protective immunity against ocular herpes simplex type 1 (HSV-1) infection. Lymphocyte-activation gene 3 (LAG-3), also known as CD223, is an immune checkpoint receptor expressed on activated CD8+ T cells.
Methods :
In this study, we determined whether LAG-3 plays a regulatory function for anti-viral T cells during ocular herpes infection and disease.
Results :
In symptomatic (SYMP) individuals, with a history of numerous episodes of recurrent ocular herpetic disease, LAG-3 is dramatically up-regulated on HSV-specific CD8+ T cells. In mice that develop ocular herpes following HSV-1 infection, LAG-3 was significantly up-regulated on CD8+ T cells infiltrating both the cornea and the trigeminal ganglia (TG), the sites of acute and latent infection, respectively. Expression level of LAG-3 on CD8+ T cells is positively correlated with the severity of ocular herpes. Blockade of LAG-3 pathway, using anti-LAG-3 mAb, three days following ocular HSV-1 infection, promoted anti-viral CD8+ T cell proliferation, cytotoxic activity and IFN-gamma production and was associated with protection from ocular herpes infection and disease. In vitro, destruction of HSV-infected corneal endothelial cells by HSV-specific CD8+ T cells was enhanced when the cornea was pretreated with anti-LAG-3 mAb. Reactivation of the virus from HSV-1 infected TG explants was enhanced following treatment with anti-LAG mAb.
Conclusions :
Taken together, these data demonstrate that the LAG-3 pathway plays an immune-regulatory role during ocular herpes infection, thereby may provide an important molecular target for enhancing immune reconstitution in human ocular herpes.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.