J. Exp. Med., Volume 188, Number 10, November 16, 1998 1967-1972

Atypical Pulmonary Eosinophilia Is Mediated by a Specific Amino Acid Sequence of the Attachment (G) Protein of Respiratory Syncytial Virus

By Paul W. Tebbey, Michael Hagen, and Gerald E. Hancock

From the Department of Immunology Research, Wyeth-Lederle Vaccines and Pediatrics, West Henrietta, New York 14586-9728

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]- 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- 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.

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