title: Human iris pigment epithelial cells suppress T-cell activation via direct cell contact.
abstract: The purposes of the present study were to investigate whether cultured human iris pigment epithelial (hIPE) cells acquire the ability to modify T-cell activation, and if so, to identify the mechanism. Human IPE cells were prepared from patients who underwent glaucoma surgery, and were cultured in RPMI 1640 medium containing 10% fetal calf serum for 4-7 days. Expression of MHC molecules and co-stimulatory molecules on cultured hIPE cells either unstimulated or stimulated with IFN-gamma was examined by FACS. In addition, peripheral blood T cells were incubated with cultured hIPE cells prepared from the same patients and anti-CD3 antibody in a transwell culture system, or in the presence of anti-PD-L1 and PD-L2 antibodies, and T cell proliferation was assessed by [3H]-thymidine incorporation. The hIPE cells inhibited anti-CD3-driven T-cell activation but the inhibition was diminished when tested in the transwell culture system, indicating that a contact-dependent mechanism is important in the immunoregulatory roles of hIPE. Although cultured hIPE cells expressed Class I and PD-L1 but not Class II or PD-L2, all these molecules were observed on hIPE cells cultured in the presence of IFN-gamma. Blocking antibodies against both PD-L1 and PD-L2 reduced the immunoregulatory activity of hIPE cells. Our data indicates that cultured hIPE cells inhibit T-cell activation by T-cell receptor ligation, which is mediated by cell-to-cell contact in part via the PD-L1 and PD-L2 pathways.
authors.affiliation: Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160 0023, Japan. ninnin@ss.iij4u.or.jp
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hattori
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kezuka
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Usui
authors.forename: Yoko
authors.initials: Y
authors.lastname: Okunuki
authors.forename: Masaru
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Maruyama
authors.forename: Mai
authors.initials: M
authors.lastname: Haneda
authors.forename: Shiroaki
authors.initials: S
authors.lastname: Shirato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Goto
mesh_terms: D015703:Antigens, CD / Q000276:immunology; D060890:B7-H1 Antigen; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D006649:Histocompatibility Antigens / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D007498:Iris / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D010857:Pigment Epithelium of Eye / Q000276:immunology*; D061027:Programmed Cell Death 1 Ligand 2 Protein; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D006649:Histocompatibility Antigens; D036341:Intercellular Signaling Peptides and Proteins; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein; D007371:Interferon-gamma