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, Jung Won Park, Satoko Miyahara, Annette Balhorn, Azzeddine Dakhama, Erwin W. Gelfand

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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 - Feb 15 2004
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Miyahara, N., Takeda, K., Kodama, T., Joetham, A., Taube, C., Park, J. W., Miyahara, S., Balhorn, A., Dakhama, A., & Gelfand, E. W. (2004). Contribution of Antigen-Primed CD8+ T Cells to the Development of Airway Hyperresponsiveness and Inflammation Is Associated with IL-13. Journal of Immunology, 172(4), 2549-2558. https://doi.org/10.4049/jimmunol.172.4.2549