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S. Sugita, Y. Futagami, Y. Yamada, S. Horie, H. Takase, M. Mochizuki; The Role of Cytotoxic T Lymphocyte Antigen-2a in Suppression of Mechanism of Retinal Pigment Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2511.
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© ARVO (1962-2015); The Authors (2016-present)
To whether soluble factors by retinal pigment epithelial cells (RPE) promote the generation of T regulatory cells in vitro.
Primary cultured RPE cells were established from normal C57BL/6 mice. T cells were co-cultured with RPE, x-irradiated, and used as regulators (RPE Treg cells). 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. Expression of cytotoxic T lymphocyte antigen-2α (CTLA-2α) and cathepsin L on RPE and T cells was evaluated with oligonucleotide microarray, RT-PCR, immune staining, western blots and flow cytometry. Recombinant mouse CTLA-2α and anti-mouse CTLA-2α antibody were used for the assay.
Cultured RPE converted CD4+ T cells into T regulatory cells (Treg cells) by producing and secreting CTLA-2α. Cultured RPE constitutively expressed CTLA-2α. CTLA-2α secreted by RPE inhibited cathepsin L in bystander T cells and the T cells were converted into Treg cells. CTLA-2α also enhanced their production of active forms of transforming growth factor beta (TGFβ). The CD4+ Treg cells greatly expressed CD25 and Foxp3 molecules, and significantly suppressed activation of T cells in vitro.
These results show that immunosuppressive factors derived from RPE cells participate in T cell suppression. Thus, the eye-derived Treg cells acquire functions that participate in the establishment of immune tolerance in the posterior segment of the eye.
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