Advances and challenges in studying the tissue‐resident T cell compartment in the human female reproductive tract

Abstract

Summary Tissue‐resident memory T cells (TRM) are considered to be central to maintaining mucosal barrier immunity and tissue homeostasis. Most of this knowledge stems from murine studies, which provide access to all organs. These studies also allow for a thorough assessment of the TRM compartment for each tissue and across tissues with well‐defined experimental and environmental variables. Assessing the functional characteristics of the human TRM compartment is substantially more difficult; thus, notably, there is a paucity of studies profiling the TRM compartment in the human female reproductive tract (FRT). The FRT is a mucosal barrier tissue that is naturally exposed to a wide range of commensal and pathogenic microbes, including several sexually transmitted infections of global health significance. We provide an overview of studies describing T cells within the lower FRT tissues and highlight the challenges of studying TRM cells in the FRT: different sampling methods of the FRT greatly affect immune cell recovery, especially of TRM cells. Furthermore, menstrual cycle, menopause, and pregnancy affect FRT immunity, but little is known about changes in the TRM compartment. Finally, we discuss the potential functional plasticity of the TRM compartment during inflammatory episodes in the human FRT to maintain protection and tissue homeostasis, which are required to ensure reproductive fitness.

CD4+T and CD8+T Cells in Uterus Exhibit Both Selective Dysfunction and Residency Signatures

“…However, much of this knowledge comes from murine researches. Little is known about T RM cells in human endometrium due to a variety of biological variables such as hormonal changes, sexual activity, and age which can influence their abundance and function [ 14 ]. To further determine similarities and discrepancies in immunological characteristics of human and mouse CD4 + T and CD8 + T cells, we recruited 20 individuals in the luteal phase and collected endometrium samples.…”

A Noninvasive Method to Sample Immune Cells in the Lower Female Genital Tract Using Menstrual Discs

“…Common methods for sampling immune cell populations in the FGT include biopsy, cytobrush, and cervicovaginal lavage (CVL) ( 18 , 19 ). Tissue collected either from biopsy or discarded surgical tissue is considered the “gold standard” for obtaining large cell yields and allows for precise sampling of anatomical sites ( 18 , 19 ).…”

A non-invasive method to sample immune cells in the lower female genital tract using menstrual discs

“…Common methods for sampling immune cell populations in the FGT include biopsy, cytobrush, and cervicovaginal lavage (CVL) 4 (18, 19). Tissue collected either from biopsy or discarded surgical tissue is considered the “gold standard” in the field for obtaining large cell yields and allows for precise sampling of anatomical sites (18, 19).…”

“…Common methods for sampling immune cell populations in the FGT include biopsy, cytobrush, and cervicovaginal lavage (CVL) 4 (18, 19). Tissue collected either from biopsy or discarded surgical tissue is considered the “gold standard” in the field for obtaining large cell yields and allows for precise sampling of anatomical sites (18, 19). This approach has identified two key T cell populations in the FGT: tissue resident memory (T RM ) 5 cells and migratory cells, which circulate between the tissue, regional lymph nodes, and peripheral blood (17, 20, 21).…”