Epitopes described in "Regulatory T cells promote early influx of CD8+ T cells in the lungs of respiratory syncytial virus-infected mice and diminish immunodominance disparities."

Article Authors:Tracy J Ruckwardt; Kathryn L Bonaparte; Martha C Nason; Barney S Graham
Article Title:Regulatory T cells promote early influx of CD8+ T cells in the lungs of respiratory syncytial virus-infected mice and diminish immunodominance disparities.
Reference Detail
Reference ID:1014092
Abstract:In addition to regulating autoimmunity and antitumor immunity, CD4(+) CD25(+) FoxP3(+) natural regulatory T (Treg) cells are global regulators of adaptive immune responses. Depletion of these cells with the anti-CD25 antibody PC61 prior to primary respiratory syncytial virus (RSV) infection was partial but had several effects on the RSV-specific CD8(+) response in a hybrid mouse model. Mediastinal lymph node and spleen epitope-specific CD8(+) T-cell responses were enhanced in Treg-cell-depleted mice at all time points following infection, but responses of Treg-cell-depleted lung show a strikingly different pattern than lymphoid organ responses, with an initial delay in the CD8(+) T-cell response. The delay in the CD8(+) T-cell response correlated with a delay both in the early phase of viral clearance and in illness in Treg-cell-depleted mice compared to isotype-treated controls. The lungs of Treg-cell-depleted mice were shown to have increased lung chemokine and cytokine levels 7 days postinfection despite lower CD8(+) T-cell responses. Following the early delay in the lung response, CD8(+) T-cell responses at later infection time points were enhanced and increased the severity of illness in depleted mice. Finally, decreasing regulatory T-cell control of the CD8(+) T-cell response had a greater effect on response of the dominant K(d)-restricted M2 epitope consisting of amino acids 82 to 90 (K(d)M2(82-90)) than on the subdominant D(b)M(187-195) epitope response, indicating that regulatory T cells modulate immunodominance disparities in epitope-specific CD8(+) T-cell responses following primary RSV infection.
Affiliations:Viral Pathogenesis Laboratory, Vaccine Research Center, National Institute of Allergy and Infections Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Reference Type:Literature
PubMed ID:19153229
Journal:J Virol
Journal Volume:83
Article Pages:3019-28
Journal ISSN:1098-5514
Article Chemical List:Cytokines
Article MeSH List:Animals; CD8-Positive T-Lymphocytes(immunology); Cell Line; Cytokines(analysis); Female; Lung(chemistry; immunology; pathology; virology); Lymph Nodes(immunology); Lymphocyte Depletion; Mice; Respiratory Syncytial Virus Infections(immunology; pathology); Respiratory Syncytial Viruses(immunology); Severity of Illness Index; Spleen(immunology); T-Lymphocytes, Regulatory(immunology)
Curation Last Updated:2015-07-30 20:29:20