Human HSV-Specific Memory CD8⁺ T_EM Cells with Unique JAK/STAT, Chemokine and Anti-Inflammatory Gene Signatures Are Associated with Asymptomatic Ocular Herpes Infection

Abstract

Purpose : A large proportion of the world population harbors herpes simplex virus type 1 (HSV-1) which causes potentially blinding recurrent herpetic disease. HSV-specific CD8⁺ T cells provide immunosurveillance of latently infected sensory neurons from which the virus sporadically reactivates from latency causing recurrent herpetic disease. However, the molecular signatures of CD8⁺ T cells that protect asymptomatic (ASYMP) individuals who never experienced any recurrent herpetic disease, remain to be elucidated.

Methods : In this study, we used Flow Cytometry and NanoString assays to compare the phenotype, the effector function, and the expression of a comprehensive panel of 579 immune genes of memory CD8⁺ T cells, that shared the same epitope-specificity, but were freshly sorted from the peripheral blood of well-characterized cohorts of ASYMP and symptomatic (SYMP) individuals, with a history of numerous episodes of recurrent herpetic disease.

Results : Regardless of the epitope specificity: (i) we detected frequent multi-functional HSV-specific effector memory CD62L^lowCD44^highCD8⁺ T_EM cells in ASYMP individuals compared to more of central memory CD62L^highCD44^highCD8⁺ T_CM cells in SYMP individuals; (ii) we found memory CD8⁺ T cells from ASYMP individuals express higher level of JAK/STAT, chemokine and anti-inflammatory genes.

Conclusions : These findings suggest that expansion of effector function of HSV-specific memory CD8⁺ T_EM cells with molecular signatures associated with T cell activation, migration and anti-inflammation play an important role in asymptomatic herpes infection in humans.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.