Polarized Uterine Epithelial Cells Preferentially Present Antigen at the Basolateral Surface: Role of Stromal Cells in Regulating Class II-Mediated Epithelial Cell Antigen Presentation

Abstract

To study Ag presentation in the female reproductive tract, DO11.10 TCR transgenic mice specific for the class II MHC-restricted OVA323–339 peptide and nontransgenic BALB/c mice were used. We report here that freshly isolated uterine epithelial cells, uterine stromal, and vaginal APCs present OVA and OVA323–339peptide to naive- and memory T cells, which is reduced when cells are incubated with Abs to CD80 and 86. To determine whether polarized primary epithelial cells present Ags, uterine epithelial cells were cultured on cell inserts in either the upright or inverted position. After reaching confluence, as indicated by high transepithelial resistance (>2000 ohms/well), Ag presentation by epithelial cells incubated with memory T cells and OVA323–339 peptide placed on the basolateral surface (inverted) was 2- to 3-fold greater than that seen with epithelial cells in contact with T cells and peptide on the apical surface (upright). In contrast, whereas freshly isolated epithelial cells process OVA, polarized epithelial cells did not. When epithelial cells grown upright on inserts were incubated with T cells and OVA323–339 peptide, coculture with either hepatocyte growth factor or conditioned stromal medium increased epithelial cell Ag presentation (∼90% higher than controls). These studies indicate that uterine stromal cells produce a soluble factor(s) in addition to a hepatocyte growth factor, which regulates epithelial cell Ag presentation. Overall, these results demonstrate that polarized epithelial cells are able to present Ags and suggest that uterine stromal cells communicate with epithelial cells via a soluble factor(s) to regulate Ag presentation in the uterus.

Profiles and technological requirements of urogenital probiotics

“…It has been suggested that there is a site-specific mucosal immune system in the female upper genital tract that differs from that described in the gastrointestinal and respiratory tracts [185,186]. Furthermore, the immune system in the upper genital tract differs from that of the lower genital tract [14,[180][181][182][183][184][185][186]. The putative immune system in the upper genital tract appears to contribute to the maintenance of an aseptic milieu; that is, this immune system inhibits the growth of microorganisms that sporadically colonize this region [181,183].…”

“…The sequelae of such inflammation in the upper genital tract would be highly detrimental to the defense and reproductive functions of the mucosal surface [184]. If the protection afforded by the epithelial barrier is compromised, however, pathogens encounter a second layer of innate defense consisting of specialized immune cells and their products [180,181]. These cells, which include macrophages, dendritic cells, neutrophils, and natural killer cells, are dispersed throughout the female genital tract, surveying that environment [181].…”

“…To add to this complexity, the various parts of the female genital tract are influenced by sex hormones during menstruation [182]. All of these components act in concert to optimize the conditions for reproduction and a successful pregnancy [108,126,[180][181][182][183][184]. The female genital tract is protected against these various…”

“…These pathogens include viruses, bacteria, fungi and parasites [14,108,126,180,181]. To add to this complexity, the various parts of the female genital tract are influenced by sex hormones during menstruation [182].…”

Paternal Antigen-Bearing Cells Transferred during Insemination Do Not Stimulate Anti-Paternal CD8+ T Cells: Role of Estradiol in Locally Inhibiting CD8+ T Cell Responses

“…responses in the FRT are suppressed by a mechanism possibly acting through an APC, and this effect can be reproduced by estradiol treatment of ovariectomized (OVX) mice (32)(33)(34)(35). Intravaginal (IVAG) immunization during estrus (but not diestrus) also reduced subsequent delayed-type hypersensitivity responses (36).…”