Assessment of the Th1/Th2 paradigm in whole blood in atopy and asthma - Increased IFN-gamma-producing CD8(+) T cells in asthma

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 i n 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 th e Th1/Th2 paradigm in atopy and asthma. Sixty-nine subjects (31 atopic asth matics, six nonatopic asthmatics, 13 atopic nonasthmatics, and 19 control s ubjects) were included in this study. Interleukin-4 (IL-4), interferon gamm a (IFN-gamma), and IL-12 were assayed in stimulated whole blood culture sup ernatants 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 cyto metry. Atopy was characterized by a higher production of IL-4, which was co rrelated to total IgE levels, and by an impairment of the T-cell capacity t o produce IFN-gamma. This impairment was correlated to the number of positi ve skin tests. In asthma, the overproduction of IL-4 was still found if ato py was present. Unexpectedly, an overproduction of IFN-gamma was found, whi ch was related to an increased capacity of CD8(+) T cells to produce IFN-ga mma. 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 sho w 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.