Epitope-specific regulatory CD4 T cells reduce virus-induced illness while preserving CD8 T-cell effector function at the site of infection.
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.
Liu
Jie
J
Vaccine Research Center, NIAID, National Institutes of Health, 40 Convent Dr., Bethesda, MD 20892-3017, USA.
Ruckwardt
Tracy J
TJ
Chen
Man
M
Nicewonger
John D
JD
Johnson
Teresa R
TR
Graham
Barney S
BS
D000818:Animals; D000956:Antigens, Viral / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology
D000956:Antigens, Viral; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053699:Interleukin-7 Receptor alpha Subunit; D022261:Respiratory Syncytial Virus Vaccines; D014763:Viral Matrix Proteins