Research Scientist IV UW Medicine (University of Washington Medicine) Seattle, Washington, United States
Disclosure(s):
Sean Hughes, MA: No financial relationships to disclose
Introduction/Rationale: Granulysin is a potent anti-microbial protein made by NK and T cells. It is abundant in cervicovaginal secretions during the follicular phase of the menstrual cycle but is nearly undetectable during the luteal phase. The mechanism and implications of this change are unknown.
Methods: Twenty-three participants collected daily vaginal swabs between the mid-follicular and mid-luteal phase and five collected them for a full cycle. Cycle phase was determined by urinary LH and serum progesterone. Endocervical cytobrushes, ectocervical biopsies, and vaginal biopsies were collected at mid-follicular and mid-luteal visits. We measured granulysin levels in the swabs by ELISA and enumerated granulysin-producing cells from the cytobrushes and biopsies by flow cytometry.
Results: Granulysin concentrations in secretions were highest during menstruation and gradually declined as much as 10,000-fold before becoming mostly undetectable during the luteal phase. In contrast, cellular expression of granulysin in the endocervix, ectocervix, and vagina was stable comparing the mid-follicular to mid-luteal phase. The most abundant granulysin-producing cell type in the mucosa was CD8 T cells, followed by NK cells. NK cells expressed granulysin at a much higher rate, but CD8 T cells were more abundant. In a minority of participants, granulysin was consistently detected in multiple luteal phase swabs; this phenomenon was associated with parity.
Conclusion: The cyclical changes in granulysin levels in cervicovaginal secretions are driven by menstruation, suggesting that the granulysin derives from uterine NK cells. In contrast, production of granulysin by resident immune cells in the cervix and vagina is independent of the menstrual cycle. These results suggest that cervicovaginal cells remain able to produce granulysin in response to microbial infection throughout the menstrual cycle, despite the large change in granulysin levels in secretions.
