Up-Regulation of Multiple CD8+ T Cell Exhaustion Pathways is Associated to Recurrent Ocular Herpes Simplex Virus Type 1 Infection
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. We found that, compared to healthy asymptomatic (ASYMP) individuals, in symptomatic (SYMP) patients the...
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| Published in: | The Journal of immunology (1950) 2020-06, Vol.205 (2), p.454-468 |
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| Main Authors: | , , , , , , , , , , , , , , |
| Format: | Article |
| Language: | eng |
| Online Access: | Get full text |
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| Summary: | 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. We found that, compared to healthy asymptomatic (ASYMP) 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 αLAG-3 and αPD-1 antagonist mAbs synergistically restored the frequency and function of antiviral CD8
+
T cells, both (
i
)
ex vivo
, in SYMP individuals and SYMP HLA-A*0201 transgenic mice; and (
ii
)
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 symptomatic herpes infection and pave the way to targeting immune checkpoints to combat recurrent ocular herpes. |
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| ISSN: | 0022-1767 1550-6606 |