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

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.

• Authors: L C Spender, T Hussell, P J Openshaw
• Journal: The Journal of general virology (J Gen Virol) Vol. 79 ( Pt 7) Pg. 1751-8 (Jul 1998) ISSN: 0022-1317 [Print] England
• PMID: 9680139 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Viral
• Antigens, Viral
• Cytokines
• HN Protein
• Immunoglobulin G
• RNA, Messenger
• Viral Envelope Proteins
• Viral Fusion Proteins
• Viral Proteins
• attachment protein G
• Interferon-gamma

Topics

• Animals
• Antibodies, Viral (immunology)
• Antigens, Viral (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cytokines (genetics)
• Female
• Flow Cytometry
• HN Protein
• Humans
• Immunoglobulin G (immunology)
• Interferon-gamma (biosynthesis, genetics)
• Kinetics
• Mice
• Mice, Inbred BALB C
• Pulmonary Eosinophilia (immunology, virology)
• RNA, Messenger
• Respiratory Syncytial Virus Infections (immunology, virology)
• Respiratory Syncytial Virus, Human (immunology)
• T-Lymphocytes (immunology, metabolism)
• Vaccination
• Viral Envelope Proteins (immunology)
• Viral Fusion Proteins (immunology)
• Viral Proteins (immunology)