Upregulation of Multiple CD8+ T Cell Exhaustion Pathways Is Associated with Recurrent Ocular Herpes Simplex Virus Type 1 Infection.
J Immunol
; 205(2): 454-468, 2020 07 15.
Article
em En
| MEDLINE
| ID: mdl-32540992
ABSTRACT
A large proportion of the world's population harbors latent HSV type 1 (HSV-1). Cross-talk between antiviral CD8+ T cells and HSV-1 appear to control latency/reactivation cycles. We found that compared with healthy asymptomatic individuals, in symptomatic (SYMP) patients, the CD8+ T cells with the same HLA-A*0201-restricted HSV-1 epitope specificities expressed multiple genes and proteins associated to major T cell exhaustion pathways and were dysfunctional. Blockade of immune checkpoints with anti-LAG-3 and anti-PD-1 antagonist mAbs synergistically restored the frequency and function of antiviral CD8+ T cells, both 1) ex vivo, in SYMP individuals and SYMP HLA-A*0201 transgenic mice; and 2) in vivo in HSV-1-infected SYMP HLA-A*0201 transgenic mice. This was associated with a significant reduction in virus reactivation and recurrent ocular herpetic disease. These findings confirm antiviral CD8+ T cell exhaustion during SYMP herpes infection and pave the way to targeting immune checkpoints to combat recurrent ocular herpes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Herpesvirus Humano 1
/
Linfócitos T CD8-Positivos
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Olho
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Herpes Simples
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2020
Tipo de documento:
Article