Vaccine-induced CD8+ T cell-dependent suppression of airway hyperresponsiveness and inflammation

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

Research output: Contribution to journalArticle

22 Citations (Scopus)

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-γ 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.

Original languageEnglish
Pages (from-to)181-190
Number of pages10
JournalJournal of Immunology
Volume183
Issue number1
DOIs
Publication statusPublished - Jul 1 2009
Externally publishedYes

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Immunization
Vaccines
Inflammation
T-Lymphocytes
Liposomes
Goblet Cells
Eosinophilia
Cytokines
Immunotherapy
Allergens
Vaccination
Asthma
DNA Vaccines
Adoptive Transfer
DNA
Metaplasia
Immunity
Therapeutics

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Vaccine-induced CD8+ T cell-dependent suppression of airway hyperresponsiveness and inflammation. / Takeda, Katsuyuki; Dow, Steven W.; Miyahara, Nobuaki; Kodama, Taku; Koya, Toshiyuki; Taube, Christian; Joetham, Anthony; Park, Jung Won; Dakhama, Azzeddine; Kedl, Ross M.; Gelfand, Erwin W.

In: Journal of Immunology, Vol. 183, No. 1, 01.07.2009, p. 181-190.

Research output: Contribution to journalArticle

Takeda, K, Dow, SW, Miyahara, N, Kodama, T, Koya, T, Taube, C, Joetham, A, Park, JW, Dakhama, A, Kedl, RM & Gelfand, EW 2009, 'Vaccine-induced CD8+ T cell-dependent suppression of airway hyperresponsiveness and inflammation', Journal of Immunology, vol. 183, no. 1, pp. 181-190. https://doi.org/10.4049/jimmunol.0803967
Takeda, Katsuyuki ; Dow, Steven W. ; Miyahara, Nobuaki ; Kodama, Taku ; Koya, Toshiyuki ; Taube, Christian ; Joetham, Anthony ; Park, Jung Won ; Dakhama, Azzeddine ; Kedl, Ross M. ; Gelfand, Erwin W. / Vaccine-induced CD8+ T cell-dependent suppression of airway hyperresponsiveness and inflammation. In: Journal of Immunology. 2009 ; Vol. 183, No. 1. pp. 181-190.
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