Am. J. Respir. Crit. Care Med., Volume 161, Number 6, June 2000, 1790-1796

Assessment of the Th1/Th2 Paradigm in Whole Blood in Atopy and Asthma
Increased IFN--producing CD8⁺ T Cells in Asthma

ANTOINE O. MAGNAN, LAURENT G. MÉLY, CHRISTOPHE A. CAMILLA, MONIQUE M. BADIER, FÉLIX A. MONTERO-JULIAN, CHANTAL M. GUILLOT, BRICE B. CASANO, SABINE J. PRATO, VINCENT FERT, PIERRE BONGRAND, and DANIEL VERVLOET

UPRES 2050, Groupe de Recherche Clinique "Pathologie respiratoire et cutanée liée à l'environnement," Service de Pneumo-Allergologie, et Centre d'Investigations Cliniques, INSERM, Assistance Publique Hôpitaux de Marseille, Hôpital Ste Marguerite, Marseilles, France; Laboratoire d'Explorations Fonctionnelles Respiratoires, Hôpital Ste Marguerite, Marseilles, France; Immunotech, Marseilles, France; and INSERM U 387, Hôpital Ste-Marguerite, Marseilles, France

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-), and IL-12 were assayed in stimulated whole blood culture supernatants by using a flow cytometer microsphere-based assay. Intracellular IL-4 and IFN- 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-. 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- was found, which was related to an increased capacity of CD8⁺ T cells to produce IFN-. The number of IFN--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--producing CD8⁺ T cells in the blood, possibly controlled by IL-12.

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