Polarized uterine epithelial cells preferentially present antigen at the basolateral surface: role of stromal cells in regulating class II-mediated epithelial cell antigen presentation.
To study Ag presentation in the female reproductive tract, DO11.10 TCR transgenic mice specific for the class II MHC-restricted OVA(323-339) peptide and non-transgenic BALB/c mice were used. We report here that freshly isolated uterine epithelial cells, uterine stromal, and vaginal APCs present OVA and OVA(323-339) peptide 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 OVA(323-339) 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 OVA(323-339) peptide, coculture with either hepatocyte growth factor or conditioned stromal medium increased epithelial cell Ag presentation (approximately 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.
Wira
Charles R
CR
Department of Physiology, Dartmouth Medical School, Lebanon, NH 03756-0001, USA. Charles.R.Wira@Dartmouth.edu
Rossoll
Richard M
RM
Young
Roger C
RC
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D016764:Cell Polarity / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D017097:Electric Impedance; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism* / Q000502:physiology; D005260:Female; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000502:physiology*; D007156:Immunologic Memory / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D014599:Uterus / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D014621:Vagina / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D017077:Culture Media, Conditioned; D000949:Histocompatibility Antigens Class II; C111389:I-Ad antigen; C111390:OVA 323-339; D010446:Peptide Fragments; D017228:Hepatocyte Growth Factor; D010047:Ovalbumin