Pulmonary eosinophilic response to respiratory syncytial virus infection in mice sensitized to the major surface glycoprotein G.
To investigate the contribution of immunity to individual respiratory syncytial (RS) virus proteins to the augmentation of pulmonary pathology, mice were scarified with recombinant vaccinia viruses (rVV) expressing individual RS virus proteins. The pulmonary response to infection with RS virus was monitored by bronchoalveolar lavage (BAL). In mice vaccinated with the major surface glycoprotein (G), 14-25% of BAL cells were eosinophils; these comprised less than 3% of BAL cells from other groups of mice after RS virus challenge. Mice sensitized to the G or fusion (F) proteins developed lung haemorrhage and those sensitized to G, F or nucleoprotein (N) showed pulmonary polymorphonucleocyte efflux. To investigate the concomitant changes in local T-cell subsets, BAL cells were stained with mAbs to CD4, CD8, CD45RB, alpha beta and gamma delta T cell receptor (TCR) proteins. Three colour flow cytometry showed that most cells were CD3+CD4+ alpha beta+gamma delta+ or CD3+CD8+ alpha beta+gamma delta-, although some CD4-CD8-SIg- cells were also identified. Most of these 'null' cells lacked CD3, but CD3+ null cells from rVV-G or -F primed mice bore either alpha beta and gamma delta TCR in approximately equal numbers. The intensity of staining for CD45RB declined rapidly after infection with RS virus on both CD4 and CD8 cells. The rate of loss of CD45RB on CD4 T cells was accelerated by prior sensitization with rVV-G, consistent with conversion to helper T cell subsets producing eosinophil-promoting cytokines. The eosinophilic reaction to RS virus infection therefore specifically reflects sensitization to G protein, but sensitization to other proteins can also cause distinct pathological effects.(ABSTRACT TRUNCATED AT 250 WORDS)
Openshaw
P J
PJ
Department of Medicine, St Mary's Hospital Medical School, London, UK.
Clarke
S L
SL
Record
F M
FM
D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology / Q000473:pathology; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D015707:HN Protein; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011995:Recombination, Genetic; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000276:immunology; D010253:Respirovirus Infections / Q000276:immunology* / Q000473:pathology; D014614:Vaccines, Synthetic / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology
D000956:Antigens, Viral; D015707:HN Protein; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D014765:Viral Vaccines; C116204:attachment protein G