Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen-induced airway hyperreactivity

Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen-induced airway hyperreactivity NATURE MEDICINE Akbari, O., Stock, P., Meyer, E., Kronenberg, M., Sidobre, S., Nakayama, T., Taniguchi, M., Grusby, M. J., DeKruyff, R. H., Umetsu, D. T. 2003; 9 (5): 582-588

Abstract

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.

View details for DOI 10.1038/nm851

View details for Web of Science ID 000182610600040

View details for PubMedID 12669034