Inverse association of peripheral blood CD4+ invariant natural killer T cells with atopy in human asthma

Invariant natural killer T (iNKT) cells have been reported to play a role in the pathogenesis of murine asthma. However, the role for iNKT cells in the pathogenesis of human asthma is not defined. In this study we aimed to determined how blood iNKT cells are associated with atopy in asthmatic individuals. Peripheral blood mononuclear cells were isolated from 45 asthmatic subjects. iNKT cells were stained with 6B11 mAb, anti-TCRvα24 mAb, or α-galactosylceramide (GalCer)–loaded CD1d− tetramer and analyzed with flow-cytometric assays. Increased serum total IgE or one or more positive skin reactions to common allergens were used as atopic indexes. Asthmatic subjects with IgE > 500 IU/ml showed lower frequency of CD4+ 6B11+ iNKT cells (p < 0.01) or CD4+ Vα24+ iNKT cells (p < 0.01) compared with subjects with IgE ≤ 500 IU/ml. Asthmatic subjects with atopy on skin tests had lower frequency of CD4+ α-GalCer–loaded CD1d− tetramer+ iNKT cells compared with those without atopy (p < 0.05). The frequency of CD4+ Vα24+ iNKT cells was negatively correlated with total IgE in asthmatic subjects (r = −0.33, p < 0.05). In summary, blood CD4+ iNKT cells were inversely associated with atopic indexes in asthmatic individuals. We hypothesize that blood CD4+ iNKT cells might behave like Th1-like iNKT cells in human asthma.