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Journal of Virology, May 2009, p. 4934-4941, Vol. 83, No. 10
0022-538X/09/$08.00+0     doi:10.1128/JVI.02140-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Characterization of Respiratory Syncytial Virus M- and M2-Specific CD4 T Cells in a Murine Model{triangledown}

Jie Liu, Tracy J. Ruckwardt, Man Chen, Teresa R. Johnson, and Barney S. Graham*

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland

Received 10 October 2008/ Accepted 24 February 2009

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 M213-223 (FKYIKPQSQFI) and M227-37 (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-Ab-restricted pattern. Construction of fluorochrome-conjugated peptide-I-Ab 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, M209-223 peptide-activated CD4 T cells reduced IFN-{gamma} and IL-2 production in M- and M2-specific CD8 T-cell responses to Db-M187-195 and Kd-M282-90 peptides more than M225-39 peptide-stimulated CD4 T cells. This correlated with the fact that I-Ab-M209-223 tetramer-positive cells responding to primary RSV infection had a much higher frequency of FoxP3 expression than I-Ab-M226-39 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-Ab tetramers allows detailed analysis of their roles in RSV pathogenesis and immunity.

* Corresponding author. Mailing address: Vaccine Research Center, NIAID, National Institutes of Health, 40 Convent Dr., Bethesda, MD 20892-3017. Phone: (301) 594-8468. Fax: (301) 480-2771. E-mail: bgraham{at}nih.gov

{triangledown} Published ahead of print on 4 March 2009.

Journal of Virology, May 2009, p. 4934-4941, Vol. 83, No. 10
0022-538X/09/$08.00+0     doi:10.1128/JVI.02140-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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