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The Journal of Immunology, 2003, 171: 4073-4080.
Copyright © 2003 by The American Association of Immunologists

Psychological Stress Exerts an Adjuvant Effect on Skin Dendritic Cell Functions In Vivo 1

Pierre Saint-Mezard*, Cyril Chavagnac*, Sophie Bosset*, Marius Ionescu{dagger}, Eric Peyron*, Dominique Kaiserlian{ddagger}, Jean-Francois Nicolas2,* and Frédéric Bérard*

* Institut National de la Santé et de la Recherche Médicale Unité 503, IFR 128, and Department of Clinical Immunology and Allergy, CHU Lyon-Sud, Lyon, France; {dagger} Laboratoire Bioderma, Lyon, France; and {ddagger} Institut National de la Santé et de la Recherche Médicale Unité 404, IFR 128, Lyon, France

Psychological stress affects the pathophysiology of infectious, inflammatory, and autoimmune diseases. However, the mechanisms by which stress could modulate immune responses in vivo are poorly understood. In this study, we report that application of a psychological stress before immunization exerts an adjuvant effect on dendritic cell (DC), resulting in increased primary and memory Ag-specific T cell immune responses. Acute stress dramatically enhanced the skin delayed-type hypersensitivity reaction to haptens, which is mediated by CD8+ CTLs. This effect was due to increased migration of skin DCs, resulting in augmented CD8+ T cell priming in draining lymph nodes and enhanced recruitment of CD8+ T cell effectors in the skin upon challenge. This adjuvant effect of stress was mediated by norepinephrine (NE), but not corticosteroids, as demonstrated by normalization of the skin delayed-type hypersensitivity reaction and DC migratory properties following selective depletion of NE. These results suggest that release of NE by sympathetic nerve termini during a psychological stress exerts an adjuvant effect on DC by promoting enhanced migration to lymph nodes, resulting in increased Ag-specific T cell responses. Our findings may open new ways in the treatment of inflammatory diseases, e.g., psoriasis, allergic contact dermatitis, and atopic dermatitis.




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