Characterization of respiratory syncytial virus M- and M2-specific CD4 T cells in a murine model.
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.
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
Johnson
Teresa R
TR
Graham
Barney S
BS
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005802:Genes, MHC Class II; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000276:immunology* / Q000472:pathogenicity; D013154:Spleen / Q000276:immunology / Q000821:virology; D014764:Viral Proteins / Q000276:immunology*
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D007371:Interferon-gamma