Contribution of antigen-primed CD8+ T cells to the development of airway hyperresponsiveness and inflammation is associated with IL-13.

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.

• Authors: Nobuaki Miyahara, Katsuyuki Takeda, Taku Kodama, Anthony Joetham, Christian Taube, Jung-Won Park, Satoko Miyahara, Annette Balhorn, Azzeddine Dakhama, Erwin W Gelfand
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 172 Issue 4 Pg. 2549-58 (Feb 15 2004) ISSN: 0022-1767 [Print] United States
• PMID: 14764728 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens
• CD8 Antigens
• Cytokines
• Interleukin-13
• Immunoglobulin E
• Ovalbumin

Topics

• Administration, Inhalation
• Adoptive Transfer
• Animals
• Antigens (administration & dosage, immunology)
• Bronchial Hyperreactivity (genetics, immunology, pathology)
• Bronchoalveolar Lavage Fluid (immunology)
• CD8 Antigens (genetics)
• CD8-Positive T-Lymphocytes (immunology, metabolism, transplantation)
• Cell Division (immunology)
• Cells, Cultured
• Cytokines (biosynthesis, metabolism)
• Female
• Immunoglobulin E (biosynthesis)
• Inflammation (genetics, immunology)
• Injections, Intraperitoneal
• Interleukin-13 (biosynthesis, deficiency, genetics, physiology)
• Lung (immunology, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Ovalbumin (administration & dosage, immunology)