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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<jats:sup>d<\/jats:sup>-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-\u03b3), RSV F<jats:sub>51-66<\/jats:sub>-specific CD4 T cells secreted interleukin-5, and mice developed pulmonary eosinophilia after RSV challenge. IFN-\u03b3-deficient mice exhibited decreased weight loss compared to wild-type controls, suggesting that IFN-\u03b3 exacerbates systemic disease. These data demonstrate that IFN-\u03b3 can have both beneficial and detrimental effects during a secondary RSV infection.<\/jats:p>","DOI":"10.1128\/jvi.01949-07","type":"journal-article","created":{"date-parts":[[2007,12,20]],"date-time":"2007-12-20T01:53:51Z","timestamp":1198115631000},"page":"2196-2207","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":39,"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"],"prefix":"10.1128","volume":"82","author":[{"given":"Elaine M.","family":"Castilow","sequence":"first","affiliation":[{"name":"Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Olson","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Iowa, Iowa City, Iowa 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David K.","family":"Meyerholz","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Iowa, Iowa City, Iowa 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Varga","sequence":"additional","affiliation":[{"name":"Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa 52242"},{"name":"Department of Microbiology, University of Iowa, Iowa City, Iowa 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.1.81"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.62.11.4232-4238.1988"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.4049\/jimmunol.161.5.2473","volume":"161","year":"1998","unstructured":"Bembridge, G. 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