Akbari O, Stock P, Meyer E, et al. Nat Med. 2003;9:582–588
Purpose of the Study.
To determine the role of natural killer T (NKT) cells in the development of asthma.
NKT cell-deficient mice were used to determine the relative contribution of NKT cells to the development of T helper type 2 (Th2) responses and allergen-induced airway hyperreactivity (AHR).
The investigators found that AHR, a cardinal feature of asthma, did not develop in the absence of NKT cells. The failure of NKT cell–deficient mice to develop AHR was not attributable to an inability of the mice to produce Th2 responses, because NKT cell-deficient mice that were immunized subcutaneously at nonmucosal sites produced normal Th2-biased responses. The failure to develop AHR could be reversed with the adoptive transfer of tetramer-purified NKT cells producing interleukin-4 and interleukin-13 to Ja281−/− mice, which lack the invariant T-cell receptor of NKT cells, or with the administration to Cd1 days−/− mice of recombinant interleukin-13, which directly affects airway smooth muscle cells.
Pulmonary NKT cells crucially regulate the development of asthma and Th2-biased respiratory immunity against nominal exogenous antigens. Therapies that target NKT cells may be clinically effective in limiting the development of AHR and asthma.
The contribution of different cell types to the development of asthma is an area of intense interest. This elegant study points to the likely importance of NKT cells in the development of allergen-induced airway hyperreactivity, a cardinal feature of asthma.