Early CD4(+) T cell help prevents partial CD8(+) T cell exhaustion and promotes maintenance of Herpes Simplex Virus 1 latency

J Immunol. 2010 Jan 1;184(1):277-86. doi: 10.4049/jimmunol.0902373. Epub 2009 Nov 30.

Abstract

HSV-specific CD8(+) T cells provide constant immunosurveillance of HSV-1 latently infected neurons in sensory ganglia, and their functional properties are influenced by the presence of latent virus. In this study, we show that ganglionic HSV-specific CD8(+) T cells exhibit a higher functional avidity (ability to respond to low epitope density) than their counterparts in noninfected lungs, satisfying a need for memory effector cells that can respond to low densities of viral epitopes on latently infected neurons. We further show that lack of CD4(+) T cell help during priming leads to a transient inability to control latent virus, which was associated with a PD-1/PD-L1 mediated reduced functional avidity of ganglionic HSV-specific CD8(+) T cells. CD4(+) T cells are not needed to maintain CD8(+) T cell memory through 34 d after infection, nor do they have a direct involvement in the maintenance of HSV-1 latency.

Publication types

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

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Flow Cytometry
  • Herpes Simplex / immunology*
  • Herpesvirus 1, Human / physiology
  • Immunologic Memory*
  • Mice
  • Reverse Transcriptase Polymerase Chain Reaction
  • Virus Latency / immunology*