Contribution of Antigen-Primed CD8+ T Cells to the Development of Airway Hyperresponsiveness and Inflammation Is Associated with IL-13

Nobuaki Miyahara, Katsuyuki Takeda, Taku Kodama, Anthony Joetham, Christian Taube, Jungwon Park, Satoko Miyahara, Annette Balhorn, Azzeddine Dakhama, Erwin W. Gelfand

Research output: Contribution to journalArticle

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Abstract

The role of Th2/CD4 T cells, which secrete IL-4, IL-5, and IL-13, in allergic disease is well established; however, the role of CD8+ T cells (allergen-induced airway hyperresponsiveness (AHR) and inflammation) is less clear. This study was conducted to define the role of Ag-primed CD8 + T cells in the development of these allergen-induced responses. CD8-deficient (CD8-/-) mice and wild-type mice were sensitized to OVA by i.p. injection and then challenged with OVA via the airways. Compared with wild-type mice, CD8-/- mice developed significantly lower airway responsiveness to inhaled methacholine and lung eosinophilia, and exhibited decreased IL-13 production both in vivo, in the bronchoalveolar lavage (BAL) fluid, and in vitro, following Ag stimulation of peribronchial lymph node (PBLN) cells in culture. Reconstitution of sensitized and challenged CD8-/- mice with allergen-sensitized CD8+ T cells fully restored the development of AHR, BAL eosinophilia, and IL-13 levels in BAL and in culture supernatants from PBLN cells. In contrast, transfer of naive CD8 + T cells or allergen-sensitized CD8+ T cells from IL-13-deficient donor mice failed to do so. Intracellular cytokine staining of lung as well as PBLN T cells revealed that CD8+ T cells were a source of IL-13. These data suggest that Ag-primed CD8+ T cells are required for the full development of AHR and airway inflammation, which appears to be associated with IL-13 production from these primed T cells.

Original languageEnglish
Pages (from-to)2549-2558
Number of pages10
JournalJournal of Immunology
Volume172
Issue number4
DOIs
Publication statusPublished - 2004 Feb 15

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CD8 Antigens
Interleukin-13
Inflammation
T-Lymphocytes
Allergens
Lymph Nodes
Eosinophilia
Bronchoalveolar Lavage
Lung
Methacholine Chloride
Interleukin-5
Bronchoalveolar Lavage Fluid
Interleukin-4
Cell Culture Techniques
Staining and Labeling
Cytokines

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Miyahara, Nobuaki ; Takeda, Katsuyuki ; Kodama, Taku ; Joetham, Anthony ; Taube, Christian ; Park, Jungwon ; Miyahara, Satoko ; Balhorn, Annette ; Dakhama, Azzeddine ; Gelfand, Erwin W. / Contribution of Antigen-Primed CD8+ T Cells to the Development of Airway Hyperresponsiveness and Inflammation Is Associated with IL-13. In: Journal of Immunology. 2004 ; Vol. 172, No. 4. pp. 2549-2558.
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abstract = "The role of Th2/CD4 T cells, which secrete IL-4, IL-5, and IL-13, in allergic disease is well established; however, the role of CD8+ T cells (allergen-induced airway hyperresponsiveness (AHR) and inflammation) is less clear. This study was conducted to define the role of Ag-primed CD8 + T cells in the development of these allergen-induced responses. CD8-deficient (CD8-/-) mice and wild-type mice were sensitized to OVA by i.p. injection and then challenged with OVA via the airways. Compared with wild-type mice, CD8-/- mice developed significantly lower airway responsiveness to inhaled methacholine and lung eosinophilia, and exhibited decreased IL-13 production both in vivo, in the bronchoalveolar lavage (BAL) fluid, and in vitro, following Ag stimulation of peribronchial lymph node (PBLN) cells in culture. Reconstitution of sensitized and challenged CD8-/- mice with allergen-sensitized CD8+ T cells fully restored the development of AHR, BAL eosinophilia, and IL-13 levels in BAL and in culture supernatants from PBLN cells. In contrast, transfer of naive CD8 + T cells or allergen-sensitized CD8+ T cells from IL-13-deficient donor mice failed to do so. Intracellular cytokine staining of lung as well as PBLN T cells revealed that CD8+ T cells were a source of IL-13. These data suggest that Ag-primed CD8+ T cells are required for the full development of AHR and airway inflammation, which appears to be associated with IL-13 production from these primed T cells.",
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Miyahara, N, Takeda, K, Kodama, T, Joetham, A, Taube, C, Park, J, Miyahara, S, Balhorn, A, Dakhama, A & Gelfand, EW 2004, 'Contribution of Antigen-Primed CD8+ T Cells to the Development of Airway Hyperresponsiveness and Inflammation Is Associated with IL-13', Journal of Immunology, vol. 172, no. 4, pp. 2549-2558. https://doi.org/10.4049/jimmunol.172.4.2549

Contribution of Antigen-Primed CD8+ T Cells to the Development of Airway Hyperresponsiveness and Inflammation Is Associated with IL-13. / Miyahara, Nobuaki; Takeda, Katsuyuki; Kodama, Taku; Joetham, Anthony; Taube, Christian; Park, Jungwon; Miyahara, Satoko; Balhorn, Annette; Dakhama, Azzeddine; Gelfand, Erwin W.

In: Journal of Immunology, Vol. 172, No. 4, 15.02.2004, p. 2549-2558.

Research output: Contribution to journalArticle

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T1 - Contribution of Antigen-Primed CD8+ T Cells to the Development of Airway Hyperresponsiveness and Inflammation Is Associated with IL-13

AU - Miyahara, Nobuaki

AU - Takeda, Katsuyuki

AU - Kodama, Taku

AU - Joetham, Anthony

AU - Taube, Christian

AU - Park, Jungwon

AU - Miyahara, Satoko

AU - Balhorn, Annette

AU - Dakhama, Azzeddine

AU - Gelfand, Erwin W.

PY - 2004/2/15

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N2 - The role of Th2/CD4 T cells, which secrete IL-4, IL-5, and IL-13, in allergic disease is well established; however, the role of CD8+ T cells (allergen-induced airway hyperresponsiveness (AHR) and inflammation) is less clear. This study was conducted to define the role of Ag-primed CD8 + T cells in the development of these allergen-induced responses. CD8-deficient (CD8-/-) mice and wild-type mice were sensitized to OVA by i.p. injection and then challenged with OVA via the airways. Compared with wild-type mice, CD8-/- mice developed significantly lower airway responsiveness to inhaled methacholine and lung eosinophilia, and exhibited decreased IL-13 production both in vivo, in the bronchoalveolar lavage (BAL) fluid, and in vitro, following Ag stimulation of peribronchial lymph node (PBLN) cells in culture. Reconstitution of sensitized and challenged CD8-/- mice with allergen-sensitized CD8+ T cells fully restored the development of AHR, BAL eosinophilia, and IL-13 levels in BAL and in culture supernatants from PBLN cells. In contrast, transfer of naive CD8 + T cells or allergen-sensitized CD8+ T cells from IL-13-deficient donor mice failed to do so. Intracellular cytokine staining of lung as well as PBLN T cells revealed that CD8+ T cells were a source of IL-13. These data suggest that Ag-primed CD8+ T cells are required for the full development of AHR and airway inflammation, which appears to be associated with IL-13 production from these primed T cells.

AB - The role of Th2/CD4 T cells, which secrete IL-4, IL-5, and IL-13, in allergic disease is well established; however, the role of CD8+ T cells (allergen-induced airway hyperresponsiveness (AHR) and inflammation) is less clear. This study was conducted to define the role of Ag-primed CD8 + T cells in the development of these allergen-induced responses. CD8-deficient (CD8-/-) mice and wild-type mice were sensitized to OVA by i.p. injection and then challenged with OVA via the airways. Compared with wild-type mice, CD8-/- mice developed significantly lower airway responsiveness to inhaled methacholine and lung eosinophilia, and exhibited decreased IL-13 production both in vivo, in the bronchoalveolar lavage (BAL) fluid, and in vitro, following Ag stimulation of peribronchial lymph node (PBLN) cells in culture. Reconstitution of sensitized and challenged CD8-/- mice with allergen-sensitized CD8+ T cells fully restored the development of AHR, BAL eosinophilia, and IL-13 levels in BAL and in culture supernatants from PBLN cells. In contrast, transfer of naive CD8 + T cells or allergen-sensitized CD8+ T cells from IL-13-deficient donor mice failed to do so. Intracellular cytokine staining of lung as well as PBLN T cells revealed that CD8+ T cells were a source of IL-13. These data suggest that Ag-primed CD8+ T cells are required for the full development of AHR and airway inflammation, which appears to be associated with IL-13 production from these primed T cells.

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