Epitope-specific regulatory CD4 T cells reduce virus-induced illness while preserving CD8 T-cell effector function at the site of infection

Jie Liu; Tracy J Ruckwardt; Man Chen; John D Nicewonger; Teresa R Johnson; Barney S Graham

doi:10.1128/JVI.00963-10

Epitope-specific regulatory CD4 T cells reduce virus-induced illness while preserving CD8 T-cell effector function at the site of infection

J Virol. 2010 Oct;84(20):10501-9. doi: 10.1128/JVI.00963-10. Epub 2010 Aug 4.

Authors

Jie Liu¹, Tracy J Ruckwardt, Man Chen, John D Nicewonger, Teresa R Johnson, Barney S Graham

Affiliation

¹ Vaccine Research Center, NIAID, National Institutes of Health, 40 Convent Dr., Bethesda, MD 20892-3017, USA.

Abstract

The role of epitope-specific regulatory CD4 T cells in modulating CD8 T-cell-mediated immunopathology during acute viral infection has not been well defined. In the murine model of respiratory syncytial virus (RSV) infection, CD8 T cells play an important role in both viral clearance and immunopathology. We have previously characterized two RSV epitope-specific CD4 T-cell responses with distinct phenotypic properties. One of them, the IA(b)M(209)-specific subset, constitutively expresses FoxP3 and modulates CD8 T-cell function in vitro. We show here that the IA(b)M(209)-specific CD4 T-cell response regulates CD8 T-cell function in vivo and is associated with diminished RSV-induced illness without affecting viral clearance at the site of infection. Achieving the optimal balance of regulatory and effector T-cell function is an important consideration for designing future vaccines.

MeSH terms

Animals
Antigens, Viral / genetics
CD8-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / pathology
Cytokines / biosynthesis
Epitopes, T-Lymphocyte* / genetics
Female
Forkhead Transcription Factors / metabolism
Interleukin-7 Receptor alpha Subunit / metabolism
Lymphocyte Depletion
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Respiratory Syncytial Virus Infections / immunology*
Respiratory Syncytial Virus Infections / metabolism
Respiratory Syncytial Virus Infections / pathology
Respiratory Syncytial Virus Vaccines / immunology
Respiratory Syncytial Viruses / genetics
Respiratory Syncytial Viruses / immunology
T-Lymphocyte Subsets / immunology
T-Lymphocyte Subsets / metabolism
T-Lymphocyte Subsets / pathology
T-Lymphocytes, Regulatory / immunology*
T-Lymphocytes, Regulatory / metabolism
T-Lymphocytes, Regulatory / pathology
Viral Matrix Proteins / genetics
Viral Matrix Proteins / immunology

Substances

Antigens, Viral
Cytokines
Epitopes, T-Lymphocyte
Forkhead Transcription Factors
Foxp3 protein, mouse
Interleukin-7 Receptor alpha Subunit
Respiratory Syncytial Virus Vaccines
Viral Matrix Proteins