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| Article Authors: | Jie Liu; Tracy J Ruckwardt; Man Chen; Teresa R Johnson; Barney S Graham |
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| Article Title: | Characterization of respiratory syncytial virus M- and M2-specific CD4 T cells in a murine model. |
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| Reference ID: | 1014058 |
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| Abstract: | CD4 T cells have been shown to play an important role in the immunity and immunopathogenesis of respiratory syncytial virus (RSV) infection. We identified two novel CD4 T-cell epitopes in the RSV M and M2 proteins with core sequences M(213-223) (FKYIKPQSQFI) and M2(27-37) (YFEWPPHALLV). Peptides containing the epitopes stimulated RSV-specific CD4 T cells to produce gamma interferon (IFN-gamma), interleukin 2 (IL-2), and other Th1- and Th2-type cytokines in an I-A(b)-restricted pattern. Construction of fluorochrome-conjugated peptide-I-A(b) class II tetramers revealed RSV M- and M2-specific CD4 T-cell responses in RSV-infected mice in a hierarchical pattern. Peptide-activated CD4 T cells from lungs were more activated and differentiated, and had greater IFN-gamma expression, than CD4 T cells from the spleen, which, in contrast, produced greater levels of IL-2. In addition, M(209-223) peptide-activated CD4 T cells reduced IFN-gamma and IL-2 production in M- and M2-specific CD8 T-cell responses to D(b)-M(187-195) and K(d)-M2(82-90) peptides more than M2(25-39) peptide-stimulated CD4 T cells. This correlated with the fact that I-A(b)-M(209-223) tetramer-positive cells responding to primary RSV infection had a much higher frequency of FoxP3 expression than I-A(b)-M2(26-39) tetramer-positive CD4 T cells, suggesting that the M-specific CD4 T-cell response has greater regulatory function. Characterization of epitope-specific CD4 T cells by novel fluorochrome-conjugated peptide-I-A(b) tetramers allows detailed analysis of their roles in RSV pathogenesis and immunity. |
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| Affiliations: | Vaccine Research Center, NIAID, National Institutes of Health, 40 Convent Dr., Bethesda, MD 20892-3017, USA. |
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| Date: | 2009 |
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| Reference Type: | Literature |
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| PubMed ID: | 19264776 |
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| Journal: | J Virol |
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| Journal Volume: | 83 |
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| Article Pages: | 4934-41 |
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| Journal ISSN: | 1098-5514 |
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| Article Chemical List: | Antigens, Viral;Epitopes, T-Lymphocyte;Interleukin-2;Recombinant Fusion Proteins;Viral Proteins;Interferon-gamma |
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| Article MeSH List: | Animals; Antigens, Viral(immunology); CD4-Positive T-Lymphocytes(immunology; virology); CD8-Positive T-Lymphocytes(immunology; virology); Cells, Cultured; Disease Models, Animal; Epitopes, T-Lymphocyte(immunology); Female; Genes, MHC Class II; Interferon-gamma(immunology); Interleukin-2(immunology); Lung(immunology; virology); Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Recombinant Fusion Proteins(immunology); Respiratory Syncytial Virus Infections(immunology; virology); Respiratory Syncytial Viruses(immunology; pathogenicity); Spleen(immunology; virology); Viral Proteins(immunology) |
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| Curation Last Updated: | 2011-10-28 20:49:13 |
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