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*Substance via MeSH
Medline Plus Health Information
*Eosinophilic Disorders
*Respiratory Syncytial Virus Infections

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Journal of Virology, March 2008, p. 2196-2207, Vol. 82, No. 5
0022-538X/08/$08.00+0     doi:10.1128/JVI.01949-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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{triangledown}

Elaine M. Castilow,1 Matthew R. Olson,2 David K. Meyerholz,3 and Steven M. Varga1,2*

Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa 52242,1 Department of Microbiology, University of Iowa, Iowa City, Iowa 52242,2 Department of Pathology, University of Iowa, Iowa City, Iowa 522423

Received 5 September 2007/ Accepted 7 December 2007

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-Ed-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 F51-66-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.

* Corresponding author. Mailing address: 3-532 Bowen Science Building, University of Iowa, Iowa City, IA 52242. Phone: (319) 335-7784. Fax: (319) 335-9006. E-mail: steven-varga{at}uiowa.edu

{triangledown} Published ahead of print on 19 December 2007.

Journal of Virology, March 2008, p. 2196-2207, Vol. 82, No. 5
0022-538X/08/$08.00+0     doi:10.1128/JVI.01949-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Meyerholz, D. K., Griffin, M. A., Castilow, E. M., Varga, S. M. (2009). Comparison of Histochemical Methods for Murine Eosinophil Detection in an RSV Vaccine-enhanced Inflammation Model. Toxicol Pathol 37: 249-255 [Abstract] [Full Text]  
  • Olson, M. R., Hartwig, S. M., Varga, S. M. (2008). The Number of Respiratory Syncytial Virus (RSV)-Specific Memory CD8 T Cells in the Lung Is Critical for Their Ability to Inhibit RSV Vaccine-Enhanced Pulmonary Eosinophilia. J. Immunol. 181: 7958-7968 [Abstract] [Full Text]  
  • Castilow, E. M., Legge, K. L., Varga, S. M. (2008). Cutting Edge: Eosinophils Do Not Contribute to Respiratory Syncytial Virus Vaccine-Enhanced Disease. J. Immunol. 181: 6692-6696 [Abstract] [Full Text]  


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