Abundant IFN-gamma production by local T cells in respiratory syncytial virus-induced eosinophilic lung disease.
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.
Respiratory Medicine, National Heart and Lung Institute, Imperial College School of Medicine at St Mary's, London, UK.
L C
LC
Spender
T
T
Hussell
P J
PJ
Openshaw
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D015707:HN Protein; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D011657:Pulmonary Eosinophilia / Q000276:immunology* / Q000821:virology; D012333:RNA, Messenger; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000821:virology; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014611:Vaccination; D014759:Viral Envelope Proteins / Q000276:immunology; D014760:Viral Fusion Proteins / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology
D000914:Antibodies, Viral; D000956:Antigens, Viral; D016207:Cytokines; D015707:HN Protein; D007074:Immunoglobulin G; D012333:RNA, Messenger; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; D014764:Viral Proteins; C116204:attachment protein G; D007371:Interferon-gamma