title: Vaccine-induced CD8+ T cell-dependent suppression of airway hyperresponsiveness and inflammation.
abstract: 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-gamma 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.
authors: Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA.
authors: Katsuyuki
authors: K
authors: Takeda
authors: Steven W
authors: SW
authors: Dow
authors: Nobuaki
authors: N
authors: Miyahara
authors: Taku
authors: T
authors: Kodama
authors: Toshiyuki
authors: T
authors: Koya
authors: Christian
authors: C
authors: Taube
authors: Anthony
authors: A
authors: Joetham
authors: Jung-Won
authors: JW
authors: Park
authors: Azzeddine
authors: A
authors: Dakhama
authors: Ross M
authors: RM
authors: Kedl
authors: Erwin W
authors: EW
authors: Gelfand
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002412:Cations / Q000008:administration & dosage / Q000378:metabolism; D016207:Cytokines / Q000502:physiology; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D006183:H-2 Antigens / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000276:immunology; D018836:Inflammation Mediators / Q000008:administration & dosage* / Q000276:immunology*; D008081:Liposomes; D016210:Methacholine Chloride / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D002412:Cations; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D008081:Liposomes; D019444:Vaccines, DNA; D016210:Methacholine Chloride; D010047:Ovalbumin