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Estrogen Blocks Early T Cell Development in the Thymus
Author(s) -
Rijhsinghani Asha G.,
Thompson Kristin,
Bhatia Sudershan K.,
Waldschmidt Thomas J.
Publication year - 1996
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/j.1600-0897.1996.tb00176.x
Subject(s) - medicine , estrogen , endocrinology , biology , il 2 receptor , lymphopoiesis , cd8 , population , t cell , cd44 , immune system , immunology , stem cell , cell , haematopoiesis , environmental health , genetics
PROBLEM: Pregnancy and estrogen are known to suppress B lymphopoiesis as well as lead to thymic involution in the mouse. Additionally, estrogen deficiency by oophorectomy reportedly causes a selective increase in the B220+ B cells in the murine bone marrow. The purpose of this study was to determine if estrogens played a regulatory role in T cell development. METHODS: The first experimental group consisted of 5–6‐week‐old Balb/c mice that received subcutaneous pellets of placebo, estriol, estradiol, or progesterone. The thymus glands were examined 2–4 weeks after treatment. The second group consisted of 6‐week‐old Balb/c mice who underwent either bilateral oophorectomy or a sham procedure. Two weeks after the surgery, extensive phenotypic characterization of the thymus and spleen cells was performed by flow cytometry using monoclonal antibodies to surface markers of T cell subsets. RESULTS: Estrogen treatment causes a dramatic reduction of thymic size and cellularity. All defined T cell subsets of CD4 and CD8 were reduced, with a disproportionate loss of CD4+CD8+ double positive cells. Examination of the triple negative (CD3‐CD4‐CD8‐) subset revealed a striking loss of TN developmental progression of the early precursor cells. Based on the expression of CD44 (pgp‐1) and CD25 (IL‐2Rα) markers, the TN thymic compartment was composed almost entirely of the earliest population (CD44+, CD25‐), with the remaining maturational stages (CD44+, CD25+; CD44‐, CD25+; CD44‐, CD25‐) depleted. In contrast, all T cell developmental stages in the thymus were found to be in normal proportions in the oophorectomized mice, with no differences in the splenic T and B cell subsets. CONCLUSIONS: The study demonstrates that estrogen but not progesterone blocks T cell development in the thymus. However, contrary to our expectation, estrogen deprivation by oophorectomy does not enhance T cell development.