Assessment of the Th1/Th2 Paradigm in Whole Blood in Atopy and Asthma

Abstract

Atopy is characterized by an immune system that is biased to T helper cell, type 2 (Th2) activation. This condition predisposes to asthma, a disease in which a Th2 activation was found in blood and lungs. However, most blood studies have considered purified cells, which might give an incomplete view of immune reactions. In this study, we assessed in whole blood cultures the Th1/Th2 paradigm in atopy and asthma. Sixty-nine subjects (31 atopic asthmatics, six nonatopic asthmatics, 13 atopic nonasthmatics, and 19 control subjects) were included in this study. Interleukin-4 (IL-4), interferon gamma (IFN-gamma), and IL-12 were assayed in stimulated whole blood culture supernatants by using a flow cytometer microsphere-based assay. Intracellular IL-4 and IFN-gamma were detected in T cells and CD8(+) T cells by flow cytometry. Atopy was characterized by a higher production of IL-4, which was correlated to total IgE levels, and by an impairment of the T-cell capacity to produce IFN-gamma. This impairment was correlated to the number of positive skin tests. In asthma, the overproduction of IL-4 was still found if atopy was present. Unexpectedly, an overproduction of IFN-gamma was found, which was related to an increased capacity of CD8(+) T cells to produce IFN-gamma. The number of IFN-gamma-producing CD8(+) T cells was related to asthma severity, to bronchial hyperresponsiveness, and to blood eosinophilia. In addition, this number was correlated to IL-12 production. These results show that in addition to the well-known Th2 inflammation in asthma, there are IFN-gamma-producing CD8(+) T cells in the blood, possibly controlled by IL-12.

T-helper cell type-2 regulation in allergic disease

“…In a mouse model of virally induced AHR and airway remodelling, there was no attenuation of these parameters in IFN-c-deficient mice [60]. Interestingly, there is evidence that IFN-c expression in peripheral blood CD8+ T-cells correlated with AHR in asthmatic subjects [61], and a recent study found that IFN-c production in cord blood CD8 T-cells predicted subsequent allergic sensitisation [62]. IFN-c-expressing lymphocytes are present in the lungs or sputum of some subjects with asthma [63,64], and it would seem likely that IFN-c-secreting cytolytic CD8+ cells would be recruited to the lung during virally triggered exacerbations.…”

Cytokine Regulation of Periportal Fibrosis in Humans Infected with Schistosoma mansoni: IFN-γ Is Associated with Protection Against Fibrosis and TNF-α with Aggravation of Disease

“…The Simultaneous Multianalyte Reagent Technology method is a flow cytometric immunoassay performed on fluorescent and Ab-coated microspheres (30), allowing the simultaneous titration of IL-1␤, IL-4, IL-6, IL-10, and IL-12p40, with a sensitivity of 0.5-1.5 pg/ml. It has been described extensively previously (31).…”

Association between asthma and female sex hormones

“…In nonatopic asthma, a neutrophil inflammatory process may occur. 18 Tregs (regulatory T cells) reduce proliferation and decrease Th2 levels and hence the inflammatory process in asthma cases. 19 Tregs are essential for induction and maintenance of tolerance against antigens.…”