Effector CD8+ T cells mediate inflammation and airway hyper-responsiveness.
Allergic asthma is a complex syndrome characterized by airway obstruction, airway inflammation and airway hyper-responsiveness (AHR). Using a mouse model of allergen-induced AHR, we previously demonstrated that CD8-deficient mice develop significantly lower AHR, eosinophilic inflammation and interleukin (IL)-13 levels in bronchoalveolar lavage fluid compared with wild-type mice. These responses were restored by adoptive transfer of antigen-primed CD8(+) T cells. Previously, two distinct populations of antigen-experienced CD8(+) T cells, termed effector (T(EFF)) and central memory (T(CM)) cells, have been described. After adoptive transfer into CD8-deficient mice, T(EFF), but not T(CM), cells restored AHR, eosinophilic inflammation and IL-13 levels. T(EFF), but not T(CM), cells accumulated in the lungs, and intracellular cytokine staining showed that the transferred T(EFF) cells were a source of IL-13. These data suggest an important role for effector CD8(+) T cells in the development of AHR and airway inflammation, which may be associated with their Tc2-type cytokine production and their capacity to migrate into the lung.
Miyahara
Nobuaki
N
Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado, USA.
Swanson
Bradley J
BJ
Takeda
Katsuyuki
K
Taube
Christian
C
Miyahara
Satoko
S
Kodama
Taku
T
Dakhama
Azzeddine
A
Ott
Vanessa L
VL
Gelfand
Erwin W
EW
D019264:Adoptive Transfer; D000485:Allergens / Q000276:immunology*; D000534:Alum Compounds; D000704:Analysis of Variance; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000473:pathology; D001991:Bronchitis / Q000276:immunology* / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D018793:Interleukin-13 / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D016210:Methacholine Chloride; D051379:Mice; D008817:Mice, Mutant Strains; D010047:Ovalbumin; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000485:Allergens; D000534:Alum Compounds; D016827:CD8 Antigens; D016207:Cytokines; D018793:Interleukin-13; C446402:ovalbumin-alum; D016210:Methacholine Chloride; D010047:Ovalbumin