title: 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.
abstract: Children that were administered a formalin-inactivated respiratory syncytial virus (FI-RSV) vaccine experienced enhanced respiratory disease, including pulmonary eosinophilia, after contracting a natural RSV infection. RSV vaccine-enhanced disease can be mimicked in BALB/c mice immunized with either FI-RSV or with a recombinant vaccinia virus (vacv) expressing the RSV attachment (G) protein. We have recently demonstrated that memory CD8 T cells directed against the RSV immunodominant M2(82-90) epitope inhibit the development of pulmonary eosinophilia in either vacvG- or FI-RSV-immunized mice by reducing the total number of Th2 cells in the lung after RSV challenge. In this study, we show that memory CD8 T cells specific to a subdominant epitope within the RSV fusion (F) protein fail to inhibit the development of pulmonary eosinophilia after RSV challenge of mice previously co-immunized with vacvF and with either vacvG or FI-RSV. We observed that the inability of RSV F(85)-specific memory CD8 T cells to inhibit the development of pulmonary eosinophilia was largely due to an inadequate total number of F(85)-specific memory CD8 T cells in the lung at early times after RSV challenge. Increasing the number of F(85)-specific memory CD8 T cells after immunization grants these cells the ability to inhibit RSV vaccine-enhanced pulmonary eosinophilia. Moreover, we demonstrate that RSV-specific memory CD8 T cells, when present in sufficient numbers, inhibit the production of the Th2-associated chemokines CCL17 and CCL22. Taken together, these results indicate that RSV-specific memory CD8 T cells may alter the trafficking of Th2 cells and eosinophils into the lung.
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Olson
authors.forename: Stacey M
authors.initials: SM
authors.lastname: Hartwig
authors.forename: Steven M
authors.initials: SM
authors.lastname: Varga
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D054414:Chemokine CCL17 / Q000276:immunology; D054422:Chemokine CCL22 / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000276:immunology* / Q000517:prevention & control; D004804:Eosinophils / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control; D022261:Respiratory Syncytial Virus Vaccines / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D015164:Vaccines, Inactivated / Q000009:adverse effects / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology
chemical_list: C499538:Ccl17 protein, mouse; C515483:Ccl22 protein, mouse; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D018984:Epitopes, T-Lymphocyte; D022261:Respiratory Syncytial Virus Vaccines; D015164:Vaccines, Inactivated; D014759:Viral Envelope Proteins; C116204:attachment protein G