Human endometrial epithelium exhibits regional specific changes throughout the menstrual cycle. This includes differential expression of HLA-DR and proliferation in the proliferative phase and apoptosis and cell-cell dissociation in the secretory/menstrual phases. Based on the premise that lymphoid aggregates in the basalis contain activated T cells, we proposed the differential interferon (IFN)-gamma secretion as a basis for preferential HLA-DR expression & inhibition of proliferation of endometrial epithelium in the basalis during the proliferative phase. Evidence-for activation of endometrial T cells preferentially localized in the basalis, secretion of IFN-gamma by these cells,induction of HLA-DR expression and inhibition of proliferation of endometrial epithelium by this cytokine all supported this concept. Furthermore, we have identified a new pathway by which the epithelial cell properties may be modulated by T cells. This novel cell-cell communication pathway consists of interaction of cells with vesicles shed from T cells that encompass T cell associated proteins including TNF-alpha. Based on these findings, we propose that the effect of T cells and their products continues in the secretory/menstrual phases and may be implicated in the apoptosis and dysochesion of endometrial epithelium during the secretory/menstrual phases. Therefore, the goals of this proposal is to examine the role of T cells in these specific attributes of epithelial cells and to study whether such epithelial cell properties are differentially regulated by the T cell signals. Clearly, these studies are essential in identifying the active role of T cells in the machinery that drives human endometrium throughout menstrual cycles and prime it for conception. Such information will also serve as a basis for understanding the T cell signals that potentially impair endometrial function resulting in such common manifestations as bleeding, abnormal menstruation and infertility.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
7R01CA046866-11
Application #
2823114
Study Section
Reproductive Endocrinology Study Section (REN)
Program Officer
Finerty, John F
Project Start
1988-12-01
Project End
1999-11-30
Budget Start
1998-09-22
Budget End
1999-11-30
Support Year
11
Fiscal Year
1998
Total Cost
Indirect Cost
Name
North Shore University Hospital
Department
Type
DUNS #
City
Manhasset
State
NY
Country
United States
Zip Code
11030