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(Journal of Leukocyte Biology. 2003;73:493-501.)
© 2003 by Society for Leukocyte Biology

Fever-like thermal conditions regulate the activation of maturing dendritic cells

Jean-Nicolas Tournier*, Anne Quesnel Hellmann*, Gaëtan Lesca*, Alain Jouan*, Emmanuel Drouet{dagger} and Jacques Mathieu*

* Département de Biologie des agents Transmissibles, Centre de Recherches du Service de Santé des Armées, La Tronche cedex, France; and
{dagger} EA 2939 GDR CNRS, "Virologie moléculaire et structurale," La Tronche, France

Correspondence: Jean-Nicolas Tournier, Centre de Recherches du Service de Santé des Armées, Département de Biologie des agents Transmissibles, BP87; F-38702 La Tronche cedex, France. E-mail: jntournier{at}crssa.net

Fever is one of the most frequent clinical signs encountered in pathology, especially with respect to infectious diseases. It is currently thought that the role of fever on immunity is limited to activation of innate immunity; however, its relevance to activation of adaptive immunity remains unclear. Dendritic cells (DCs) that behave as sentinels of the immune system provide an important bridge between innate and adaptive immunity. To highlight the role of fever on adaptive immunity, we exposed murine bone marrow-derived lipopolysaccharide (LPS)- or live bacteria-maturing DCs over a 3-h period to 37°C or to fever-like thermal conditions (39°C or 40°C). At these three temperatures, we measured the kinetics of cytokine production and the ability of DCs to induce an allogeneic mixed lymphocyte reaction. Our results show that short exposure of DCs to temperatures of 39°C or 40°C differentially increased the secretion of interleukin (IL)-12p70 and decreased the secretion of IL-10 and tumor necrosis factor {alpha} by maturing DCs. These fever-like conditions induced a regulation of cytokine production at the single-cell level. In addition, short-term exposed LPS-maturing DCs to 39°C induced a stronger reaction with allogeneic CD4+ T cells than maturing DCs incubated at 37°C. These results provide evidence that temperature regulates cytokine secretion and DC functions, both of which are of particular importance in bacterial diseases.

Key Words: hyperthermia • danger signal • cytokine • Salmonella typhimurium




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