Estradiol enhances primary antigen-specific CD4 T cell responses and Th1 development in vivo. Essential role of estrogen receptor α expression in hematopoietic cells

Authors

  • Arlette Maret,

    1. INSERM U397, Institut Louis Bugnard, CHU Rangueil, Toulouse, France
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    • The first three authors contributed equally to this work.

  • Jérôme D. Coudert,

    1. Institut National de la Santé et de la Recherche Médicale (INSERM) U563, Centre de Physiopathologie de Toulouse Purpan, Institut Claude de Préval, Hôpital Purpan, Toulouse, France
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  • Lucile Garidou,

    1. Institut National de la Santé et de la Recherche Médicale (INSERM) U563, Centre de Physiopathologie de Toulouse Purpan, Institut Claude de Préval, Hôpital Purpan, Toulouse, France
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  • Gilles Foucras,

    1. Institut National de la Santé et de la Recherche Médicale (INSERM) U563, Centre de Physiopathologie de Toulouse Purpan, Institut Claude de Préval, Hôpital Purpan, Toulouse, France
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  • Pierre Gourdy,

    1. INSERM U397, Institut Louis Bugnard, CHU Rangueil, Toulouse, France
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  • Andrée Krust,

    1. Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS-INSERM-ULP-Collège de France, Illkirch, France
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  • Sonia Dupont,

    1. Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS-INSERM-ULP-Collège de France, Illkirch, France
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  • Pierre Chambon,

    1. Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS-INSERM-ULP-Collège de France, Illkirch, France
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  • Philippe Druet,

    1. Institut National de la Santé et de la Recherche Médicale (INSERM) U563, Centre de Physiopathologie de Toulouse Purpan, Institut Claude de Préval, Hôpital Purpan, Toulouse, France
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  • Francis Bayard,

    1. INSERM U397, Institut Louis Bugnard, CHU Rangueil, Toulouse, France
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  • Jean-Charles Guéry

    Corresponding author
    1. Institut National de la Santé et de la Recherche Médicale (INSERM) U563, Centre de Physiopathologie de Toulouse Purpan, Institut Claude de Préval, Hôpital Purpan, Toulouse, France
    • INSERM U563, Hôpital Purpan, Place du Dr. Baylac, F-31 059 Toulouse, France Fax: +33-5-6177-9291
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Abstract

It is widely accepted that females have superior immune responses than males, but the ways by which sex hormones may enhance T cell responses are still poorly understood. In the present study,we analyzed the effect of estrogens on CD4 T cell activation and differentiation after immunization with exogenous antigens. We show that administration of low doses of 17ß-estradiol (E2) to castrated female mice results in a striking increase of antigen-specific CD4 T cell responses and in the selective development of IFN-γ-producing cells. Quantitative assessment of the frequency of T cells bearing a public TCR ß chain CDR3 motif demonstrated that the clonal size of primary antigen-specific CD4 T cells was dramatically increased in immune lymph nodes from E2-treated mice. By usingmice with disrupted estrogen receptor (ER) α or ß genes, we show that ERα, but not ERβ, was necessary for the enhanced E2-driven Th1 cell responsiveness. Furthermore, ERα expressionin hematopoietic cells was essential, since E2 effects on Th1 responses were only observed in mice reconstituted with bone marrow cells from ERα+/+, but not ERα-deficient mice. These results demonstrate that estrogen administration promotes strong antigen-specific Th1 cell responses in a mechanism that requires functional expression of ERα in hematopoietic cells.

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