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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 Eosinophilia¹

Matthew R. Olson^*, Stacey M. Hartwig^* and Steven M. Varga^2,*,

^* Department of Microbiology and Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242

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 F₈₅-specific memory CD8 T cells to inhibit the development of pulmonary eosinophilia was largely due to an inadequate total number of F₈₅-specific memory CD8 T cells in the lung at early times after RSV challenge. Increasing the number of F₈₅-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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Grant R01 AI-063520 from the National Institutes of Health (to S.M.V.).

² Address correspondence and reprint requests to Dr. Steven Varga, 3–532 B.S.B., Department of Microbiology, 51 Newton Road, University of Iowa, Iowa City, IA 52242. E-mail address: steven-varga{at}uiowa.edu

³ Abbreviations used in this paper: RSV, respiratory syncytial virus; FI-RSV, formalin inactivated-RSV; vacv, vaccinia virus; G, RSV attachment protein; F, RSV fusion protein; ICS, intracellular cytokine staining; BAL, bronchoalveolar lavage; DC, dendritic cell; β-gal, β-galactosidase; MFI, mean fluorescence intensity.