Localization of T Cells, Interferon-Gamma and HLA-DR in Eutopic and Ectopic Human Endometrium

Abstract

Immunologic mechanisms are implicated in the pathogenesis of endometriosis and endometriosis-associated reproductive failure. The purpose of this study was to describe key immune response elements in eutopic and ectopic endometrium and to test the hypothesis that expression of CD3-positive T cells, the T-helper 1-type cytokine, IFN-gamma, and the antigen presentation marker, HLA-DR, vary throughout the menstrual cycle in eutopic endometrium and are more abundantly expressed in ectopic than in eutopic endometrium. Eutopic and ectopic endometrium obtained at hysterectomy from 7 women with endometriosis were compared with hysterectomy specimens from 7 women with adenomyosis and 10 women without endometriosis or endometrial pathology. Tissues were formalin-fixed, paraffin-embedded, sectioned and stained using the biotin-streptavidin-alkaline phosphatase technique and antibodies to human CD3, IFN-gamma, and HLA-DR. Eutopic endometrial samples were histologically divided into menses (n = 5), proliferative (n = 9), and secretory (n = 10) phases. Positive control tissues (spleen) and negative controls (no primary antibody) were used in each experiment. T cells, IFN-gamma and HLA-DR-positive cells were observed in eutopic endometrial samples throughout the menstrual cycle. Glandular epithelium was CD3-negative except for CD3-positive cells surrounding and occasionally interdigitating between glandular epithelium. Glandular epithelium was IFN-gamma-positive and HLA-DR-positive in all phases except the proliferative phase. Staining was more often observed in the basalis than in the functionalis layer, ranging from patchy staining to the entire gland. T cells, IFN-gamma, and HLA-DR-positive stromal cells were more abundant in secretory endometrium than in proliferative samples. CD3, IFN-gamma, and HLA-DR-positive cells were scattered throughout the myometrium and concentrated in vessels. Higher intensity staining was observed in ectopic than in eutopic endometrium, with CD3 and HLA-DR-positive cells forming aggregates around IFN-gamma and HLA-DR-positive glands. The intensity of IFN-gamma staining in ectopic endometrium was similar to the intensity of staining observed in menstrual and late secretory basalis samples from eutopic endometrium. The results of this observational study suggest that activated T cells, IFN-gamma and upregulation of antigen presentation may play a role in normal endometrial physiology. The increased number of T cells, expression of IFN-gamma, and enhanced antigen presentation in ectopic compared to eutopic endometrium support the concept that cellular immune activation is involved in endometriosis and its sequelae.