Reevaluating the CD8 T-cell response to herpes simplex virus type 1: involvement of CD8 T cells reactive to subdominant epitopes

J Virol. 2009 Mar;83(5):2237-45. doi: 10.1128/JVI.01699-08. Epub 2008 Dec 10.

Abstract

In C57BL/6 (B6) mice, most herpes simplex virus (HSV)-specific CD8 T cells recognize a strongly immunodominant epitope on glycoprotein B (gB498) and can inhibit HSV type 1 (HSV-1) reactivation from latency in trigeminal ganglia (TG). However, half of the CD8 T cells retained in latently infected TG of B6 mice are not gB498 specific and have been largely ignored. The following observations from our current study indicate that these gB498-nonspecific CD8 T cells are HSV specific and may contribute to the control of HSV-1 latency. First, following corneal infection, OVA257-specific OT-1 CD8 T cells do not infiltrate the infected TG unless mice are simultaneously immunized with OVA257 peptide, and then they are not retained. Second, 30% of CD8 T cells in acutely infected TG that produce gamma interferon in response to HSV-1 stimulation directly ex vivo are gB498 nonspecific, and these cells maintain an activation phenotype during viral latency. Finally, gB498-nonspecific CD8 T cells are expanded in ex vivo cultures of latently infected TG and inhibit HSV-1 reactivation from latency in the absence of gB498-specific CD8 T cells. We conclude that many of the CD8 T cells that infiltrate and are retained in infected TG are HSV specific and potentially contribute to maintenance of HSV-1 latency. Identification of the viral proteins recognized by these cells will contribute to a better understanding of the dynamics of HSV-1 latency.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Viral / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Herpes Simplex / immunology*
  • Herpes Simplex / virology
  • Herpesvirus 1, Human / immunology*
  • Herpesvirus 1, Human / physiology
  • Interferon-gamma / immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Trigeminal Ganglion / immunology
  • Trigeminal Ganglion / virology
  • Viral Envelope Proteins / immunology
  • Virus Latency

Substances

  • Antigens, Viral
  • Epitopes, T-Lymphocyte
  • Viral Envelope Proteins
  • glycoprotein B, Simplexvirus
  • Interferon-gamma