NKT cells have a role in human asthma

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A new study shows that CD4⁺ natural killer T cells which produce TH2 cytokines play a prominent pathogenic role in human asthma.

The recently identified subgroup of T cells, CD1d-restricted natural killer T (NKT) cells, have a prominent role in the development of allergen-induced airway hyperreactivity in mouse models of allergic asthma. However, the role of this subgroup of T cells in human asthma has been unclear. Now, a study published in The New England Journal of Medicine shows that CD1d-restricted NKT cells do indeed have an important role in human asthma.

Human NKT cells express an invariant T-cell receptor alpha -chain (TCR alpha ), as well as CD4 or CD8 or neither co-receptor, and are therefore referred to as invariant NKT (iNKT)cells. iNKT cells respond to glycolipid antigens presented by antigen-presenting cells in the context of CD1d and produce both T helper 1 (T_H1) and T_H2 cytokines. To examine the role of these cells in asthma, the frequency and distribution of CD1d-restricted iNKT cells in bronchoalveolar-lavage fluid from the lungs of 14 patients with asthma was determined using two methods: flow cytometry after incubation with the monoclonal antibody 6B11 (which is specific for the iNKT-cell TCR alpha ) and/or with CD1d-tetramers loaded with alpha -galactosylceramide (which are also specific for human iNKT cells); and reverse transcription PCR of the invariant TCR.

Large numbers of iNKT cells were found in the bronchoalveolar-lavage fluid from patients with asthma. Indeed, a high proportion of the CD4⁺ T cells that were present expressed the invariant TCR, indicating that they were actually iNKT cells. Interestingly, these observations seem to be specific to patients with asthma, as the numbers of iNKT cells detected in the bronchoalveolar-lavage fluid from patients with sarcoidosis — a multisystem disorder that mainly affects the lungs — were similar to the numbers found in healthy individuals.

The iNKT cells from the lungs of patients with asthma produced the T_H2 cytokines interleukin-4 (IL-4) and IL-13 but produced very small amounts of interferon- gamma . By contrast, iNKT cells from healthy individuals or patients with sarcoidosis produced all three cytokines.

Therefore, a subgroup of iNKT cells — which express CD4 and produce T_H2 cytokines — are recruited to or are clonally expanded in the lungs of patients with asthma and produce cytokines that are essential to the development of this disorder.

Olive Leavy

References

Akbari, O. et al. CD4⁺ invariant T-cell-receptor⁺ natural killer T cells in bronchial asthma. N. Engl. J. Med. 354, 1117–1129 (2006) | Article | PubMed |