Journal article
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
Journal of virology, Vol.82(5), pp.2196-2207
03/2008
DOI: 10.1128/JVI.01949-07
PMCID: PMC2258940
PMID: 18094193
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.
Details
- Title: Subtitle
- 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
- Creators
- Elaine M Castilow - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, USA. steven-varga@uiowa.eduMatthew R OlsonDavid K MeyerholzSteven M Varga
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.82(5), pp.2196-2207
- DOI
- 10.1128/JVI.01949-07
- PMID
- 18094193
- PMCID
- PMC2258940
- NLM abbreviation
- J Virol
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Grant note
- R01 AI063520 / NIAID NIH HHS AI 063520 / NIAID NIH HHS
- Language
- English
- Date published
- 03/2008
- Academic Unit
- Graduate College Admin and Gen; Microbiology and Immunology; Pathology
- Record Identifier
- 9984083287602771
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