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Lbachir BenMohamed, Swayam Prakash, Ruchi Srivastava, Nisha Dhanushkodi, Pierre-Gregoire A Coulon; Up-Regulation of Multiple CD8+ T Cell Exhaustion Pathways is Associated to Recurrent Ocular Herpes Simplex Virus Type 1 Infection. Invest. Ophthalmol. Vis. Sci. 2021;62(8):910.
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© ARVO (1962-2015); The Authors (2016-present)
A large proportion of the world’s population harbors latent herpes simplex virus type 1 (HSV-1). Crosstalk between antiviral CD8+ T cells and HSV-1 appear to control latency/reactivation cycles.
In the present study, we compared the transcriptome, phenotype, and function of memory CD8+ T cells, sharing the same HLA-A*0201-restricted HSV-1 epitope-specificities freshly isolated from peripheral blood and trigeminal ganglia (TG) of HSV-1 infected ASYMP and SYMP patients and HLA transgenic (Tg) mice, respectively.
We report that HSV-specific CD8+ T cells from SYMP patients are phenotypically and functionally exhausted, highly co-expressing LAG-3 with three others inhibitory receptors while being defective in expression of functional markers. Moreover, the blocking of LAG-3 and PD-1 synergistically restored anti-viral CD8+ T cell responses, reduced HSV-1 reactivation from latently-infected TG, and reduced UV-B induced recurrent ocular herpetic infection and disease in latently-infected HLA-A*0201 transgenic mice.
These findings confirm antiviral CD8+ T cell exhaustion during symptomatic herpes infection and pave the way to targeting immune checkpoints to combat recurrent ocular herpes.
This is a 2021 ARVO Annual Meeting abstract.
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