Immune cells in the female reproductive tract

Abstract

The female reproductive tract has two main functions: protection against microbial challenge and maintenance of pregnancy to term. The upper reproductive tract comprises the fallopian tubes and the uterus, including the endocervix, and the lower tract consists of the ectocervix and the vagina. Immune cells residing in the reproductive tract play contradictory roles: they maintain immunity against vaginal pathogens in the lower tract and establish immune tolerance for sperm and an embryo/fetus in the upper tract. The immune system is significantly influenced by sex steroid hormones, although leukocytes in the reproductive tract lack receptors for estrogen and progesterone. The leukocytes in the reproductive tract are distributed in either an aggregated or a dispersed form in the epithelial layer, lamina propria, and stroma. Even though immune cells are differentially distributed in each organ of the reproductive tract, the predominant immune cells are T cells, macrophages/dendritic cells, natural killer (NK) cells, neutrophils, and mast cells. B cells are rare in the female reproductive tract. NK cells in the endometrium significantly expand in the late secretory phase and further increase their number during early pregnancy. It is evident that NK cells and regulatory T (Treg) cells are extremely important in decidual angiogenesis, trophoblast migration, and immune tolerance during pregnancy. Dysregulation of endometrial/decidual immune cells is strongly related to infertility, miscarriage, and other obstetric complications. Understanding the immune system of the female reproductive tract will significantly contribute to women's health and to success in pregnancy.

Keywords: Endometrium; Leukocyte; Natural killer cells; Pregnancy; Regulatory T cells; Reproductive tract.

Figure 1

Distribution of major leukocytes in the female reproductive tract in premenopausal women. There are some discrepancies in the proportion of each leukocyte population, since several reports have been published using different study designs. Most data represent leukocyte populations in all phases of the menstrual cycle. T, T cells; B, B cells; NK, natural killer cells; Mφ, macrophages; DC, dendritic cells. Data were collected from Givan et al. (4), Salamonsen and Woolley (13), and Trifonova et al. (1).

Figure 2

Secretion of antimicrobial molecules in the female reproductive tract in the periovulatory period. High estrogen concentration significantly affects the production of antimicrobial peptides and proinflammatory cytokines which are differentially regulated in the upper and the lower reproductive tracts (3). SLPI, secretory leukocyte peptidase inhibitor.

Figure 3

Cyclic fluctuation of endometrial leukocytes during the menstrual cycle. Immune cells in the endometrium are indirectly regulated by ovarian sex steroid hormones. Several leukocytes are significantly increased in the premenstrual phase, but some cells do not fluctuate during the menstrual cycle. The density of leukocyte population is expressed as -, +, ++, and ++ +, which represent 0%, 1~2%, 3~5%, and 6~15% of total numbers of endometrial cells, respectively. Data were collected from Salamonsen and Woolley (13), Flynn et al. (18), and Givan et al. (4).