title: Estradiol enhances primary antigen-specific CD4 T cell responses and Th1 development in vivo. Essential role of estrogen receptor alpha expression in hematopoietic cells.
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 17beta-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-gamma-producing cells. Quantitative assessment of the frequency of T cells bearing a public TCR beta 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 using mice with disrupted estrogen receptor (ER) alpha or beta genes, we show that ERalpha, but not ERbeta, was necessary for the enhanced E2-driven Th1 cell responsiveness. Furthermore, ERalpha expression in hematopoietic cells was essential, since E2 effects on Th1 responses were only observed in mice reconstituted with bone marrow cells from ERalpha+/+, but not ERalpha-deficient mice. These results demonstrate that estrogen administration promotes strong antigen-specific Th1 cell responses in a mechanism that requires functional expression of ERalpha in hematopoietic cells.
authors.affiliation: INSERM U397, Institut Louis Bugnard, CHU Rangueil, Toulouse, France.
authors.forename: Arlette
authors.initials: A
authors.lastname: Maret
authors.forename: Jérôme D
authors.initials: JD
authors.lastname: Coudert
authors.forename: Lucile
authors.initials: L
authors.lastname: Garidou
authors.forename: Gilles
authors.initials: G
authors.lastname: Foucras
authors.forename: Pierre
authors.initials: P
authors.lastname: Gourdy
authors.forename: Andrée
authors.initials: A
authors.lastname: Krust
authors.forename: Sonia
authors.initials: S
authors.lastname: Dupont
authors.forename: Pierre
authors.initials: P
authors.lastname: Chambon
authors.forename: Philippe
authors.initials: P
authors.lastname: Druet
authors.forename: Francis
authors.initials: F
authors.lastname: Bayard
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Guéry
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D018390:Gene Targeting; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010052:Ovariectomy; D011828:Radiation Chimera; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D011960:Receptors, Estrogen / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013047:Specific Pathogen-Free Organisms; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects*
chemical_list: D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; C499308:Rag2 protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011960:Receptors, Estrogen; C064655:V(D)J recombination activating protein 2; D015847:Interleukin-4; D004958:Estradiol; D007371:Interferon-gamma