Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen-induced airway hyperreactivity.
Using natural killer T (NKT) cell-deficient mice, we show here that allergen-induced airway hyperreactivity (AHR), a cardinal feature of asthma, does not develop in the absence of V(alpha)14i NKT cells. The failure of NKT cell-deficient mice to develop AHR is not due to an inability of these mice to produce type 2 T-helper (Th2) responses because NKT cell-deficient mice that are immunized subcutaneously at non-mucosal sites produce normal Th2-biased responses. The failure to develop AHR can be reversed by the adoptive transfer of tetramer-purified NKT cells producing interleukin (IL)-4 and IL-13 to Ja281(-/-) mice, which lack the invariant T-cell receptor (TCR) of NKT cells, or by the administration to Cd1d(-/-) mice of recombinant IL-13, which directly affects airway smooth muscle cells. Thus, pulmonary V(alpha)14i NKT cells crucially regulate the development of asthma and Th2-biased respiratory immunity against nominal exogenous antigens. Therapies that target V(alpha)14i NKT cells may be clinically effective in limiting the development of AHR and asthma.
Akbari
Omid
O
Division of Immunology and Allergy, Department of Pediatrics, Stanford University, Stanford, California, USA.
Stock
Philippe
P
Meyer
Everett
E
Kronenberg
Mitchell
M
Sidobre
Stephane
S
Nakayama
Toshinori
T
Taniguchi
Masaru
M
Grusby
Michael J
MJ
DeKruyff
Rosemarie H
RH
Umetsu
Dale T
DT
D019264:Adoptive Transfer; D000485:Allergens / Q000276:immunology*; D000818:Animals; D018949:Antigens, CD1 / Q000502:physiology; D055610:Antigens, CD1d; D016535:Bronchial Hyperreactivity / Q000209:etiology*; D018793:Interleukin-13 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C
D000485:Allergens; D018949:Antigens, CD1; D055610:Antigens, CD1d; D018793:Interleukin-13; D015847:Interleukin-4