Abundant IFN-gamma production by local T cells in respiratory syncytial virus-induced eosinophilic lung disease

L C Spender, T Hussell, P J Openshaw (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    40 Citations (Scopus)

    Abstract

    Respiratory syncytial virus (RSV) is a frequent cause of severe lung disease in young children. Primed T cells are required for virus clearance, but are causally implicated in the enhanced pathology seen following RSV infection of some infants and experimental animals vaccinated against the virus. In BALB/c mice, vaccination with recombinant vaccinia virus expressing the viral attachment protein (G) leads to pulmonary eosinophilia during subsequent infection, which indirect evidence suggests may be due to CD4+ Th2 cells. The production of IFN-gamma, IL-2, -4, -5 and -10 cytokine mRNA by RT-PCR and intracellular cytokines by flow cytometry following RSV challenge of vaccinated mice were therefore compared. Lung eosinophilia was associated with enhanced local recruitment of CD4+ cells in G sensitized mice, while CD8+ cells dominated in mice vaccinated with the viral fusion protein (F) or second matrix protein (M2). Lung eosinophilia was also associated with a localized reduction in IFN-gamma and increased IL-4 and IL-5 mRNA transcription as well as elevated RSV specific IgG1 antibody production. Th2 cytokine protein production by T cells showed no apparent change. Although IFN-gamma production diminished in eosinophilic mice, it remained the major cytokine found in lung T cells. It was concluded that lung eosinophilia can develop despite abundant IFN-gamma production by local T cells, but is associated with a shift in the balance between Th2 and Th1 cytokine production.

    Original languageEnglish
    Pages (from-to)1751-1758
    Number of pages8
    JournalJournal of General Virology
    Volume79
    DOIs
    Publication statusPublished - Jul 1998

    Keywords

    • Animals
    • Antibodies, Viral
    • Antigens, Viral
    • CD4-Positive T-Lymphocytes
    • CD8-Positive T-Lymphocytes
    • Cytokines
    • Female
    • Flow Cytometry
    • HN Protein
    • Humans
    • Immunoglobulin G
    • Interferon-gamma
    • Kinetics
    • Mice
    • Mice, Inbred BALB C
    • Pulmonary Eosinophilia
    • RNA, Messenger
    • Respiratory Syncytial Virus Infections
    • Respiratory Syncytial Virus, Human
    • T-Lymphocytes
    • Vaccination
    • Viral Envelope Proteins
    • Viral Fusion Proteins
    • Viral Proteins
    • Journal Article
    • Research Support, Non-U.S. Gov't

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