Contribution of antigen-primed CD8+ T cells to the development of airway hyperresponsiveness and inflammation is associated with IL-13.
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.
Miyahara
Nobuaki
N
Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Takeda
Katsuyuki
K
Kodama
Taku
T
Joetham
Anthony
A
Taube
Christian
C
Park
Jung-Won
JW
Miyahara
Satoko
S
Balhorn
Annette
A
Dakhama
Azzeddine
A
Gelfand
Erwin W
EW
D000280:Administration, Inhalation; D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016827:CD8 Antigens / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D005260:Female; D007073:Immunoglobulin E / Q000096:biosynthesis; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D007274:Injections, Intraperitoneal; D018793:Interleukin-13 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000276:immunology / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*
D000941:Antigens; D016827:CD8 Antigens; D016207:Cytokines; D018793:Interleukin-13; D007073:Immunoglobulin E; D010047:Ovalbumin