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In humans, T cells expressing the CD161 molecule NKR-P1A constitute around 20% of the circulating CD3+ cells and are potentially immunoregulatory in several diseases. Their role in asthma is not well known, but they could participate in asthma attacks. To determinate whether activation of CD161+ T cells and their cytokine production correlate with clinical status of asthma, we analysed blood samples from asthma attack patients (AAP) and stable asthma patients (SAP) in comparison with healthy non-atopic controls (HC). There was a significant higher baseline expression of CD69 on T cells from AAP and the difference was more notorious on CD161+ T cells; upregulation of CD69 was observed on both CD161− and CD161+ T cells driven by Dermatophagoides pteronyssinus crude extract, whereas polyclonal stimulation with phorbol 12-myristate 13-acetate plus ionomycin predominantly induced IFN- γ but no IL-4, IL-5 and IL-13 by CD161+ T cells in all groups; upon polyclonal stimulation, there were more CD161+ T cells producing IFN- γ and less CD161− T cells producing this cytokine, contrasting with the opposite results observed in SAP and HC groups. Our results indicate that, during asthma attack, CD161+ T cells are activated and are able to produce predominantly IFN- γ but no Th2 cytokines. We hypothesize that during an asthma attack, IFN- γ produced by CD161+ T cells could help to reestablish the Th1/Th2 equilibrium. These observations may contribute to the understanding of the immune mechanisms involved in asthma attacks. [ABSTRACT FROM AUTHOR]