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

Tissue-resident memory T cells (T_RM ) 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 T_RM compartment for each tissue and across tissues with well-defined experimental and environmental variables. Assessing the functional characteristics of the human T_RM compartment is substantially more difficult; thus, notably, there is a paucity of studies profiling the T_RM 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 T_RM cells in the FRT: different sampling methods of the FRT greatly affect immune cell recovery, especially of T_RM cells. Furthermore, menstrual cycle, menopause, and pregnancy affect FRT immunity, but little is known about changes in the T_RM compartment. Finally, we discuss the potential functional plasticity of the T_RM compartment during inflammatory episodes in the human FRT to maintain protection and tissue homeostasis, which are required to ensure reproductive fitness.