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

  • Author(s): Prakash, Swayam
  • Roy, Soumyabrata
  • Srivastava, Ruchi
  • Coulon, Pierre-Gregoire
  • Dhanushkodi, Nisha R
  • Vahed, Hawa
  • Jankeel, Allen
  • Geertsema, Roger
  • Amezquita, Cassandra
  • Nguyen, Lan
  • Messaoudi, Ilhem
  • Burkhardt, Amanda M
  • BenMohamed, Lbachir
  • et al.

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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