CD3+ CD8+ CTL activity within the human female reproductive tract: influence of stage of the menstrual cycle and menopause

Abstract

The human female reproductive tract (RT) has been analyzed by others with respect to NK cell cytolytic activity, but not CD3+ T cell (CTL) cytolytic activity. Here, we describe the cytolytic capacity of mucosal CD3+ T cells both longitudinally within the RT (Fallopian tube, uterine endometrium, endocervix, ectocervix, and vaginal mucosa) and temporally throughout the menstrual cycle, using a redirected lysis assay system. Cytolysis by CD3+ CD8+ T cells is found throughout the RT and appears to be hormonally regulated, since in the uterine endometrium, the capacity for CD3+ T cell cytolytic activity is present during the proliferative phase of the menstrual cycle and absent during the subsequent secretory (postovulatory) phase. In contrast, in postmenopausal women the entire RT, including the uterus, retains the capacity for strong CD3+ T cell cytolytic activity. These findings suggest that the high levels of estradiol and progesterone present during days 14 to 28 of the menstrual cycle down-regulate CTL activity in the uterus. As a consequence, the absence of this activity may allow implantation of a semiallogeneic embryo that would otherwise be rejected. Further, these studies indicate that CTL activity is regulated differentially in different regions of the RT, persisting in the cervix and vagina throughout the menstrual cycle.