Gamma delta (γδ) T cells in the female reproductive tract: active participants or indifferent bystanders in reproductive success?

Abstract

Summary The female reproductive tract accommodates and balances the unique immunological challenges of protection from sexually transmitted pathogens and tolerance of the fetus and placenta in pregnancy. Leukocytes in the female reproductive tract actively engage in extensive maternal adaptations that are imperative for embryo implantation, placental development, and fetal growth support. γδ T cells are abundant at many mucosal sites in the body, where they provide protection against pathogens and cancer, and have roles in tissue renewal and homeostasis. In this review, we summarize studies in humans and rodents showing that γδ T cells are prevalent in the female reproductive tract and fluctuate in response to hormone changes across the reproductive cycle. Emerging evidence points to a link between changes in their abundance and molecular repertoire in the uterus and pregnancy disorders including recurrent miscarriage and preterm birth. However, defining the precise functional role of female reproductive tract γδ T cells and understanding their physiological significance in reproduction and pregnancy have remained elusive. Here, we critically analyze whether reproductive tract γδ T cells could be active participants in reproductive events—or whether their principal function is immune defense, in which case they may compromise pregnancy success unless adequately regulated.