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Vaccine-Induced CD8⁺ T Cell-Dependent Suppression of Airway Hyperresponsiveness and Inflammation^1,2

Katsuyuki Takeda^*, Steven W. Dow, Nobuaki Miyahara^*, Taku Kodama^*, Toshiyuki Koya^*, Christian Taube^*, Anthony Joetham^*, Jung-Won Park^*, Azzeddine Dakhama^*, Ross M. Kedl and Erwin W. Gelfand^3,*

^* Department of Pediatrics, Division of Cell Biology, National Jewish Health, Denver, CO 80206; Department of Microbiology, Immunology, and Pathology, Colorado State University, Ft. Collins, CO 80523; and Integrated Department of Immunology, University of Colorado, Denver, CO 80206

Suppressing the abnormalities associated with asthma has been difficult to accomplish using immunotherapy or vaccination once the disease is established. The effector cells necessary for effective immunization/vaccination and immunotherapy of asthma are also not well understood. Therefore, we vaccinated allergen (OVA)-sensitized mice to determine whether therapeutic immunization could suppress airway hyperresponsiveness (AHR) and inflammation and to identify key immune effector cells and cytokines. Mice were immunized with a vaccine comprised of Ag and cationic liposome-DNA complexes (CLDC), a vaccine which has previously been shown to elicit strong CD4⁺ and CD8⁺ T cell responses and activation of Th1 immunity. We showed that immunization with the OVA-CLDC vaccine significantly suppressed AHR, eosinophilia, goblet cell metaplasia, and Th2 cytokine production. In contrast, immunization with CLDC alone suppressed eosinophilia and Th2 cytokine production, but failed to suppress AHR and goblet cell changes. Using adoptive transfer experiments, we found that suppression of AHR was mediated by Ag-specific CD8⁺ T cells and was dependent on IFN- production by the transferred T cells. Thus, we conclude that generation of strong, allergen-specific CD8⁺ T cell responses by immunization may be capable of suppressing AHR and allergic airway inflammation, even in previously sensitized and challenged mice.

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 The project described was supported by National Institutes of Health Grants HL-36577, HL-61005, and AI-77609.

² The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health.

³ Address correspondence and reprint requests to Dr. Erwin W. Gelfand, National Jewish Health, 1400 Jackson Street, Denver, CO 80206. E-mail address: gelfande{at}njhealth.org

⁴ Abbreviations used in this paper: CLDC, cationic liposome-DNA complex; AHR, airway hyperresponsiveness; BAL, bronchoalveolar lavage; MCh, methacholine; PAS, periodic acid-Schiff; RL, lung resistance; WT, wild type.