Abstract
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.