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J Virol. 2008 Mar;82(5):2196-207. Epub 2007 Dec 19.

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.

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  • 1Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, USA. steven-varga@uiowa.edu

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.

PMID:
18094193
[PubMed - indexed for MEDLINE]
PMCID:
PMC2258940
Free PMC Article

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