The role of steroids in the proliferation and differentation of endometrial epithelium is extensively studied. In contrast, the function of lymphoid cells that are normally present in human endometrium and may have local effects on endometrial epithelium is unknown. The possible mechanism(s) of interaction of epithelial cells with lymphoid cells (lympho-epithelial interaction) is also not known. Thus, it is the application's long term objective to determine the influence of signals of endometrial lymphoid cells (conditioned medium of endometrial T lymphocytes and cytokines) in the HLA-DR expression and proliferation of endometrial epithelium, the possible modulating influences of steroids (estrogen and progesterone) in these responses and the possible role(s) of cytokine induced HLA-DR molecules on endometrial epithelium in the binding of endometrial lymphoid (T) cells. The elements of the hypothesis will be tested in primary cultures of endometrial epithelial cells derived from human endometrium, a human carcinoma cell line, """"""""EnCa101AE"""""""" derived from a well differentiated adenocarcinoma of human endometrium and in cloned cells of this cell line. The cloned ECC1I cells are sensitive to estrogen in regard to its progesterone receptor induction and mitogenic effects as well as to cytokine """"""""IFN-gamma"""""""" in regard to its HLA-DR inducing and cytostatic effects. The endometrial T lymphocytes are isolated from stromal fraction of endometrium after isolation of glands. The expression of HLA-DR molecules will be monitored by immunostaining, by flow cytometry and by western blotting. The proliferation of epithelial cells is monitored by cell counting and immunostaining for markers of growth and incorporation of BrdU """"""""a thymidine analog that incorporates into cells in S-phase of the cycle"""""""". Studying the underlying signals of the expression of HLA-DR molecules and proliferation of human endometrial epithelium and investigating the role(s) of HLA-DR molecules in the binding of endometrial lymphoid cells is significant in understanding the normal responses of human endometrium and in approaches to endometrial diseases.
