Activation and inactivation of antiviral CD8 T cell responses during murine pneumorvirus infection

E.A.W. Claassen, P.A. van der Kant

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    40 Citations (Scopus)

    Abstract

    Pneumonia virus of mice (PVM) is a natural pathogen of mice and has been proposed as a tractable model for the replication of a pneumovirus in its natural host, which mimics human infection with human respiratory syncytial virus (RSV). PVM infection in mice is highly productive in terms of virus production compared with the situation seen with RSV in mice. Because RSV suppresses CD8 T cell effector function in the lungs of infected mice, we have investigated the nature of PVM-induced CD8 T cell responses to study pneumovirus-induced T cell responses in a natural virus-host setting. PVM infection was associated with a massive influx of activated CD8 T cells into the lungs. After identification of three PVM-specific CD8 T cell epitopes, pulmonary CD8 T cell responses were enumerated. The combined frequency of cytokine-secreting CD8 T cells specific for the three epitopes was much smaller than the total number of activated CD8 T cells. Furthermore, quantitation of the CD8 T cell response against one of these epitopes (residues 261¿270 from the phosphoprotein) by MHC class I pentamer staining and by in vitro stimulation followed by intracellular IFN- and TNF- staining indicated that the majority of pulmonary CD8 specific for the P261 epitope were deficient in cytokine production. This deficient phenotype was retained up to 96 days postinfection, similar to the situation in the lungs of human RSV-infected mice. The data suggest that PVM suppresses T cell effector functions in the lungs.
    Original languageEnglish
    Pages (from-to)6597-6604
    JournalThe Journal of Immunology
    Volume175
    Issue number10
    Publication statusPublished - 2005

    Keywords

    • respiratory syncytial virus
    • recombinant vaccinia virus
    • pneumonia virus
    • paramyxovirus infection
    • protective immunity
    • peptide motifs
    • messenger-rna
    • memory cells
    • host-defense
    • m2 protein

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