July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Blockade of Lymphocyte activation gene-3 (LAG-3) Pathway Improved the Size and Protective Function of Herpes Simplex Virus-Specific CD8+ T cells against Ocular Herpes Infection and Disease
Author Affiliations & Notes
  • Anthony B Nesburn
    Gavin Herbert Eye Institute, University of California, Irvine, Los Angeles, California, United States
  • Ruchi Srivastava
    Gavin Herbert Eye Institute, University of California, Irvine, Los Angeles, California, United States
  • Roy Soumyabrata
    Gavin Herbert Eye Institute, University of California, Irvine, Los Angeles, California, United States
  • Lbachir BenMohamed
    Gavin Herbert Eye Institute, University of California, Irvine, Los Angeles, California, United States
  • Footnotes
    Commercial Relationships   Anthony Nesburn, None; Ruchi Srivastava, None; Roy Soumyabrata, None; Lbachir BenMohamed, None
  • Footnotes
    Support  This work is supported by Public Health Service Research R01 Grants EY026103, EY019896 and EY024618 from National Eye Institute (NEI) and R21 Grant AI110902 from National Institutes of allergy and Infectious Diseases (NIAID) (to L.BM.), by Research R01 Grant AI093548 (to A.Z.), and in part by The Discovery Center for Eye Research (DCER) and the Research to Prevent Blindness (RPB) unrestricted departmental grant.
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 520. doi:https://doi.org/
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      Anthony B Nesburn, Ruchi Srivastava, Roy Soumyabrata, Lbachir BenMohamed; Blockade of Lymphocyte activation gene-3 (LAG-3) Pathway Improved the Size and Protective Function of Herpes Simplex Virus-Specific CD8+ T cells against Ocular Herpes Infection and Disease. Invest. Ophthalmol. Vis. Sci. 2018;59(9):520. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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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.

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