Unique molecular signatures of antiviral memory CD8+ T cells associated with asymptomatic recurrent ocular herpes

Swayam Prakash; Soumyabrata Roy; Ruchi Srivastava; Pierre Gregoire Coulon; Nisha R. Dhanushkodi; Hawa Vahed; Allen Jankeel; Roger Geertsema; Cassandra Amezquita; Lan Nguyen; Ilhem Messaoudi; Amanda M. Burkhardt; Lbachir BenMohamed

doi:10.1038/s41598-020-70673-z

Unique molecular signatures of antiviral memory CD8⁺ T cells associated with asymptomatic recurrent ocular herpes

Swayam Prakash
, Soumyabrata Roy
, Ruchi Srivastava
, Pierre Gregoire Coulon
, Nisha R. Dhanushkodi
, Hawa Vahed
, Allen Jankeel
, Roger Geertsema
, Cassandra Amezquita
, Lan Nguyen
, Ilhem Messaoudi
, Amanda M. Burkhardt
, Lbachir BenMohamed

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

The nature of antiviral CD8⁺ T cells associated with protective and pathogenic herpes simplex virus type 1 (HSV-1) infections remains unclear. We compared the transcriptome, phenotype, and function of memory CD8⁺ T cells, sharing the same HSV-1 epitope-specificities, from infected HLA-A*0201 positive symptomatic (SYMP) vs. asymptomatic (ASYMP) individuals and HLA-A*0201 transgenic rabbits. Compared to higher frequencies of multifunctional effector memory CD8⁺ T_EM cells in ASYMP individuals, the SYMP individuals presented dysfunctional CD8⁺ T_EM cells, expressing major exhaustion pathways. Compared to protected ASYMP HLA transgenic rabbits, the trigeminal ganglia of non-protected SYMP HLA transgenic rabbits had higher frequencies of dysfunctional tissue-resident CD8⁺ T_RM cells. Moreover, blockade of T cell exhaustion pathways restored the function of CD8⁺ T cells, reduced virus reactivation, and diminished recurrent disease in HLA transgenic rabbits. These findings reveal unique molecular signatures of protective CD8⁺ T cells and pave the way for T-cell-based immunotherapy to combat recurrent ocular herpes.

Original language	English
Article number	13843
Journal	Scientific Reports
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41598-020-70673-z
State	Published - Dec 1 2020

Bibliographical note

Publisher Copyright:
© 2020, The Author(s).

Funding

This work is supported by Public Health Service Research Grants EY026103, EY019896 and EY024618 from the National Eye Institute (NEI) and Grants AI150091, AI143348, AI147499, AI143326, AI138764, AI124911 and AI110902 from the National Institutes of Allergy and Infectious Diseases (NIAID) and in part by The Discovery Center for Eye Research (DCER) and the Research to Prevent Blindness (RPB) Grant. This work is dedicated to the memory of late Professor Steven L. Wechsler "Steve" (1948-2016), whose numerous pioneering works on herpes infection and immunity laid the foundation for this line of research. We thank the NIH Tetramer Facility (Emory University, Atlanta, GA, USA) for providing the Tetramers used in this study.

Funders	Funder number
Discovery Center for Eye Research
Public Health Service Biomedical Research Support	EY019896, EY024618
National Eye Institute/National Institutes of Health	AI124911, AI110902, AI143326, AI143348, EY026103, AI138764, AI147499
National Institute of Allergy and Infectious Diseases	R01AI150091
Research to Prevent Blindness

ASJC Scopus subject areas

General

Access to Document

10.1038/s41598-020-70673-z

Cite this

Prakash, S., Roy, S., Srivastava, R., Coulon, P. G., Dhanushkodi, N. R., Vahed, H., Jankeel, A., Geertsema, R., Amezquita, C., Nguyen, L., Messaoudi, I., Burkhardt, A. M., & BenMohamed, L. (2020). Unique molecular signatures of antiviral memory CD8⁺ T cells associated with asymptomatic recurrent ocular herpes. Scientific Reports, 10(1), Article 13843. https://doi.org/10.1038/s41598-020-70673-z

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abstract = "The nature of antiviral CD8+ T cells associated with protective and pathogenic herpes simplex virus type 1 (HSV-1) infections remains unclear. We compared the transcriptome, phenotype, and function of memory CD8+ T cells, sharing the same HSV-1 epitope-specificities, from infected HLA-A*0201 positive symptomatic (SYMP) vs. asymptomatic (ASYMP) individuals and HLA-A*0201 transgenic rabbits. Compared to higher frequencies of multifunctional effector memory CD8+ TEM cells in ASYMP individuals, the SYMP individuals presented dysfunctional CD8+ TEM cells, expressing major exhaustion pathways. Compared to protected ASYMP HLA transgenic rabbits, the trigeminal ganglia of non-protected SYMP HLA transgenic rabbits had higher frequencies of dysfunctional tissue-resident CD8+ TRM cells. Moreover, blockade of T cell exhaustion pathways restored the function of CD8+ T cells, reduced virus reactivation, and diminished recurrent disease in HLA transgenic rabbits. These findings reveal unique molecular signatures of protective CD8+ T cells and pave the way for T-cell-based immunotherapy to combat recurrent ocular herpes.",

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Prakash, S, Roy, S, Srivastava, R, Coulon, PG, Dhanushkodi, NR, Vahed, H, Jankeel, A, Geertsema, R, Amezquita, C, Nguyen, L, Messaoudi, I, Burkhardt, AM & BenMohamed, L 2020, 'Unique molecular signatures of antiviral memory CD8⁺ T cells associated with asymptomatic recurrent ocular herpes', Scientific Reports, vol. 10, no. 1, 13843. https://doi.org/10.1038/s41598-020-70673-z

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AU - Messaoudi, Ilhem

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AU - BenMohamed, Lbachir

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