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Blood, 15 March 2005, Vol. 105, No. 6, pp. 2415-2420. Prepublished online as a Blood First Edition Paper on September 21, 2004; DOI 10.1182/blood-2004-07-2819. This Article Full Text (PDF) All Versions of this Article: 2004-07-2819v1 105/6/2415    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Gourdy, P. Articles by Herbelin, A. Search for Related Content PubMed PubMed Citation Articles by Gourdy, P. Articles by Herbelin, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 27, 2004 Accepted September 10, 2004 Relevance of sexual dimorphism to regulatory T cells: estradiol promotes IFN- production by invariant natural killer T cells Pierre Gourdy, Luiza M Araujo, Ren Zhu, Barbara Garmy-Susini, Severine Diem, Henrik Laurell, Maria Leite-de-Moraes, Michel Dy, Jean Francois Arnal, Francis Bayard, and Andre Herbelin* Institut L. Bugnard, CHU Rangueil, INSERM U589, Toulouse, France CNRS UMR 8147 and Paris V, Hopital Necker, Paris, France * Corresponding author; email: herbelin{at}necker.fr. Mechanisms accounting for gender dimorphism during immune responses are still poorly understood. Since invariant Natural Killer T (iNKT) cells exert important regulatory functions through their capacity to produce both Th1 and Th2 cytokines, we addressed the question whether these activities could be modulated by sexual hormones. We found that in vivo challenge with the specific ligand of iNKT cells, -GalCer, induced significantly higher levels of IFN- in the serum of female than in male mice, while IL-4 production was not modified. In support of a crucial role of ovarian hormones in this phenomenon, a significant decrease of serum IFN- levels occured in ovariectomized females, in response to treatment with -GalCer, while orchidectomy affected neither IFN- nor IL-4 serum concentrations in males. The implication of estrogens in this selective enhancement of IFN- production by iNKT cells was demonstrated by: 1) the increased -GalCer-induced IFN- synthesis by iNKT cells upon both in vitro and in vivo exposure to estradiol; 2) the abolition of the sex-linked difference in -GalCer-induced IFN- release in estrogen receptor -deficient mice. These results provide the first evidence that estrogens influence iNKT cells leading to this gender dimorphism in their cytokine production profile. 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