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BACKGROUND: Endometriosis is a chronic disease affecting 6–10% of women of reproductive age. It is associated with subfertility in 35–50% of women. Altered endometrial receptivity secondary to changes in endometrial immunity has been proposed as a possible mechanism of endometriosis-associated subfertility. However, to date the exact mechanism and the role of certain immune cells in the endometrium remain unclear. AIM: To determine whether the characteristics and distribution of CD8+ T cells (CD8T) in the endometrium can help us reveal immunological factors relevant to endometriosis-associated subfertility, providing a potential rationale for future treatment strategies. METHODS: To ascertain the known roles of CD8T in endometriosis, we have undertaken a systematic review that was registered with PROSPERO in January 2021. We then performed immunofluorescence immunohistochemistry on eutopic endometrial tissue samples from endometriosis patients and controls with and without subfertility, in the mid-secretory phase of the menstrual cycle (n=20). RESULTS: Our systematic review included 22 papers of sufficient quality. It either revealed no difference (n=4) or an increased concentration (n=4) of CD8T in eutopic endometrium of patients when compared to healthy controls. An additional study found a decreased concentration of naïve and central memory CD8T while the concentration of tissue resident memory CD8T was increased. The literature lacks studies investigating intraepithelial and regulatory CD8T. Using confocal microscopy, we have identified CD8T in the endometrial environment and characterized their proliferative and activation status. CD8+ cells were found inserted into endometrial glands, which we hypothesize to be intraepithelial CD8T CONCLUSION: Existing evidence of CD8T in eutopic endometrium is scarce and of low-quality, with no consensus on differences in concentration between endometriosis patients and healthy controls and limited data on their proliferative and activation status. Given the limited insights into some phenotypes, our research will focus on identifying intraepithelial and regulatory CD8T subtypes using flow cytometry.



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reproductive immunology, endometriosis, subfertility, CD8+ T cells, intraepithelial lymphocytes, tissue resident memory T cells, regulatory T cells