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Estradiol enhances primary antigen-specific CD4 T cell responses and Th1 development in vivo. Essential role of estrogen receptor alpha expression in hematopoietic cells
- Source :
- European journal of immunology. 33(2)
- Publication Year :
- 2003
-
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.
- Subjects :
- CD4-Positive T-Lymphocytes
medicine.medical_specialty
T cell
Ovariectomy
Receptors, Antigen, T-Cell, alpha-beta
Immunology
Amino Acid Motifs
Biology
Interferon-gamma
Mice
Immune system
Internal medicine
medicine
Immunology and Allergy
Cytotoxic T cell
Animals
Estrogen Receptor beta
IL-2 receptor
Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
Estrogen receptor beta
Bone Marrow Transplantation
Mice, Knockout
Mice, Inbred BALB C
Dose-Response Relationship, Drug
Estradiol
ZAP70
GATA3
Estrogen Receptor alpha
Th1 Cells
Hematopoietic Stem Cells
Cell biology
Specific Pathogen-Free Organisms
DNA-Binding Proteins
Mice, Inbred C57BL
medicine.anatomical_structure
Endocrinology
Receptors, Estrogen
Radiation Chimera
Gene Targeting
Female
Interleukin-4
Lymph Nodes
Estrogen receptor alpha
hormones, hormone substitutes, and hormone antagonists
Subjects
Details
- ISSN :
- 00142980
- Volume :
- 33
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- European journal of immunology
- Accession number :
- edsair.doi.dedup.....888da4585766e15126080d73d1d205fd