Estrogen blocks early T cell development in the thymus.
OBJECTIVE
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-2R alpha) 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.
Rijhsinghani
A G
AG
Department of Obstetrics and Gynecology, University of Iowa, College of Medicine, Iowa City, USA.
Thompson
K
K
Bhatia
S K
SK
Waldschmidt
T J
TJ
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004967:Estrogens / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology*; D013950:Thymus Gland / Q000033:anatomy & histology / Q000166:cytology*; D013997:Time Factors
D004967:Estrogens; D011374:Progesterone