Atypical pulmonary eosinophilia is mediated by a specific amino acid sequence of the attachment (G) protein of respiratory syncytial virus.
We analyzed the immune responses evoked by a series of overlapping peptides to better understand the molecular basis for respiratory syncytial virus (RSV) G protein-induced eosinophilia in BALB/c mice. In vitro stimulation of spleen cells from natural G protein-primed mice showed dominant proliferative and cytokine (interferon [IFN]-gamma and interleukin [IL]-5) responses to a peptide encompassing amino acids 184-198. Mice vaccinated with peptide 184- 198 conjugated to keyhole limpet hemocyanin showed significant pulmonary eosinophilia (39.5%) after challenge with live RSV. In contrast, mice immunized with a peptide (208-222) conjugate associated with induction of IFN-gamma secreting spleen cells did not exhibit pulmonary eosinophilia after challenge. The in vivo depletion of CD4(+) cells abrogated pulmonary eosinophilia in mice vaccinated with the peptide 184-198 conjugate, whereas the depletion of CD8(+) cells had a negligible effect. Therefore, we have identified an association between peptide 184- 198 of natural G protein and the CD4(+) T cell-mediated induction of pulmonary eosinophilia after live RSV challenge. Out of 43 human donors, 6 provided peripheral blood mononuclear cells that showed reactivity to G protein from RSV A2, 3 of which responded to peptide 184- 198. The results have important implications for the development of a vaccine against RSV.
Tebbey
P W
PW
Department of Immunology Research, Wyeth-Lederle Vaccines and Pediatrics, West Henrietta, New York 14586-9728, USA.
Hagen
M
M
Hancock
G E
GE
D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000276:immunology; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D011657:Pulmonary Eosinophilia / Q000276:immunology / Q000821:virology*; D012136:Respiratory Syncytial Viruses / Q000378:metabolism*; D013154:Spleen / Q000276:immunology; D014611:Vaccination; D014764:Viral Proteins / Q000378:metabolism*
D016207:Cytokines; D010446:Peptide Fragments; D014764:Viral Proteins; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin