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Open Access item GITR contributes to the systemic adjuvanticity of the Escherichia coli heat-labile enterotoxin

Authors:Iglesias, Marcos
Santiuste, Inés
Merino, Ramón
Merino, Jesús
Keywords:Costimulation, Costimulation, Vaccination
Issue Date:Mar-2010
Publisher:Wiley-VCH
Citation:European Journal of Immunology 40(3): 754-763 (2010)
Abstract:The Escherichia coli heat-labile enterotoxin (LT) possesses a powerful mucosal and systemic adjuvant effect. However, little is known about the cellular and molecular basis of the immunostimulatory activity of LT at the mucosal level, and even less information is available on the mechanisms underlying its systemic adjuvant activity. In this study, we show that distinct mechanisms are responsible for the parenteral and mucosal adjuvanticity of LT. Indeed, the systemic administration of LT upregulates the expression of glucocorticoid-induced TNFR-related protein (GITR), but not other activation markers, in naive T cells. Using WT and GITR-deficient mice and LT and its enzymatically inactive mutant LTK63 as adjuvants, we show that the induction of GITR expression in T cells accounts for the systemic immunostimulatory capacity of LT, which requires an intact enzymatic activity. In contrast, the mucosal administration of LT does not induce GITR expression on Peyer's patche T cells and accordingly no differences are observed in the mucosal adjuvanticity of LT between WT and GITR-deficient mice. Altogether, our results demonstrate the distinct effect of LT after parenteral administration when compared with the mucosal delivery, and describe a new mechanism of LT adjuvanticity related to its ability to induce the expression of GITR in CD4+ T cells.
Description:El pdf del artículo es el manuscrito de autor.-- et al.
Publisher version (URL):http://dx.doi.org/10.1002/eji.200939865
URI:http://hdl.handle.net/10261/49738
ISSN:0014-2980
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Appears in Collections:(IBBTEC) Artículos

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