title: Differential role of gamma interferon in inhibiting pulmonary eosinophilia and exacerbating systemic disease in fusion protein-immunized mice undergoing challenge infection with respiratory syncytial virus.
abstract: Secondary exposure to respiratory syncytial virus (RSV) can lead to immunopathology and enhanced disease in vaccinated individuals. Vaccination with individual RSV proteins influences the type of secondary RSV-specific immune response that develops upon challenge RSV infection, as well as the extent of immunopathology. RSV-specific memory CD4 T cells can directly contribute to immunopathology through their cytokine production. Immunization of BALB/c mice with a recombinant vaccinia virus (vv) expressing the attachment (G) protein of RSV results in pulmonary eosinophilia upon RSV challenge, whereas immunization of mice with a vv expressing the fusion (F) protein does not. We analyzed the CD4 T-cell response to an I-E(d)-restricted CD4 T-cell epitope within the F protein of RSV corresponding to amino acids 51 to 66 in an effort to better understand the similarities and differences in the immune response elicited by the G versus the F protein. Vaccination with the G protein induces a mixture of RSV G-specific Th1 and Th2 cells with a restricted T-cell receptor repertoire. In contrast, we demonstrate here that immunization with the F protein elicits a broad repertoire of RSV F-specific CD4 T cells that predominantly exhibit a Th1 phenotype. However, in the absence of gamma interferon (IFN-gamma), RSV F(51-66)-specific CD4 T cells secreted interleukin-5, and mice developed pulmonary eosinophilia after RSV challenge. IFN-gamma-deficient mice exhibited decreased weight loss compared to wild-type controls, suggesting that IFN-gamma exacerbates systemic disease. These data demonstrate that IFN-gamma can have both beneficial and detrimental effects during a secondary RSV infection.
authors: Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, USA. steven-varga@uiowa.edu
authors: Elaine M
authors: EM
authors: Castilow
authors: Matthew R
authors: MR
authors: Olson
authors: David K
authors: DK
authors: Meyerholz
authors: Steven M
authors: SM
authors: Varga
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000502:physiology*; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011657:Pulmonary Eosinophilia / Q000473:pathology / Q000517:prevention & control*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology
chemical_list: D011993:Recombinant Fusion Proteins; D014765:Viral Vaccines; D007371:Interferon-gamma