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

Producción científica: Article › revisión exhaustiva

4 Citas (Scopus)

Resumen

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.

Idioma original	English
Número de artículo	13843
Publicación	Scientific Reports
Volumen	10
N.º	1
DOI	https://doi.org/10.1038/s41598-020-70673-z
Estado	Published - dic 1 2020

Nota bibliográfica

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

Financiación

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.

Financiadores	Número del financiador
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

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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), Artículo 13843. https://doi.org/10.1038/s41598-020-70673-z

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

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, n.º 1, 13843. https://doi.org/10.1038/s41598-020-70673-z

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AU - BenMohamed, Lbachir

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