Maintenance of T cell function in the face of chronic antigen stimulation and repeated reactivation for a latent virus infection

J Immunol. 2012 Mar 1;188(5):2173-8. doi: 10.4049/jimmunol.1102719. Epub 2012 Jan 23.

Abstract

Persisting infections are often associated with chronic T cell activation. For certain pathogens, this can lead to T cell exhaustion and survival of what is otherwise a cleared infection. In contrast, for herpesviruses, T cells never eliminate infection once it is established. Instead, effective immunity appears to maintain these pathogens in a state of latency. We used infection with HSV to examine whether effector-type T cells undergoing chronic stimulation retained functional and proliferative capacity during latency and subsequent reactivation. We found that latency-associated T cells exhibited a polyfunctional phenotype and could secrete a range of effector cytokines. These T cells were also capable of mounting a recall proliferative response on HSV reactivation and could do so repeatedly. Thus, for this latent infection, T cells subjected to chronic Ag stimulation and periodic reactivation retain the ability to respond to local virus challenge.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / transplantation
  • CD8-Positive T-Lymphocytes / virology
  • Chronic Disease
  • Epitopes, T-Lymphocyte / administration & dosage
  • Epitopes, T-Lymphocyte / immunology
  • Epitopes, T-Lymphocyte / toxicity*
  • Ganglia, Sensory / enzymology
  • Ganglia, Sensory / immunology
  • Ganglia, Sensory / pathology
  • Granzymes / biosynthesis
  • Herpes Simplex / immunology*
  • Herpes Simplex / pathology
  • Herpes Simplex / virology*
  • Herpesvirus 1, Human / immunology*
  • Herpesvirus 1, Human / pathogenicity
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Viral Envelope Proteins / administration & dosage
  • Viral Envelope Proteins / toxicity*
  • Virus Activation / immunology*
  • Virus Latency / immunology*

Substances

  • Epitopes, T-Lymphocyte
  • Viral Envelope Proteins
  • glycoprotein B, human herpesvirus 1
  • Granzymes