| First Author | Sugita S | Year | 2006 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 47 |
| Issue | 12 | Pages | 5376-84 |
| PubMed ID | 17122127 | Mgi Jnum | J:123098 |
| Mgi Id | MGI:3717055 | Doi | 10.1167/iovs.05-1354 |
| Citation | Sugita S, et al. (2006) B7+ iris pigment epithelial cells convert T cells into CTLA-4+, B7-expressing CD8+ regulatory T cells. Invest Ophthalmol Vis Sci 47(12):5376-84 |
| abstractText | PURPOSE: To determine whether iris PE (IPE) promotes the generation of regulatory T-cells (Tregs) with cell contact via B7-2/CTLA-4 interactions. METHODS: T cells were cocultured with IPE cells obtained from eyes of normal and B7-deficient mice, x-irradiated, and used as regulators. IPE T regulator cells (IPE Tregs) of normal and CD28- or CTLA-4-deficient mice were established. Target bystander T cells were established from normal splenic T cells with anti-CD3 antibodies. T-cell activation was assessed for proliferation by [3H]-thymidine incorporation. Neutralizing anti-B7-1 and/or B7-2 antibodies, anti-CTLA-4 antibodies, CTLA-4-Ig fusion proteins were used to abolish regulatory function. IPE-exposed CD8+ T cells were evaluated for expression of B7, CTLA-4, and Foxp3 by using RT-PCR and flow cytometry. CD8+ IPE Tregs were depleted of B7-2+ and CTLA-4+ T cells and assayed for suppressive activity by adding them to bystander T cells. RESULTS: T cells acquired T regulatory activity when exposed to cultured IPE. Ciliary body PE cells did not promote conversion of T cells into Tregs. IPE converted CD8+, but not CD4+, T cells into Tregs by direct cell contact. In the conversion, IPE and responding T cells must both express endogenously synthesized B7-1 and B7-2, and the T cells must also express CTLA-4. Expression of CD28 molecules was not necessary for Treg generation. In addition, the CD8+ Tregs that fully suppress activation of bystander T cells expressed Foxp3. CONCLUSIONS: IPE cells promote conversion of T cells into Tregs solely through a contact-dependent mechanism. T cells exposed to IPE cells acquire full regulatory capacity. |
