Role of ocular pigment epithelial cells in immune privilege

Abstract

The ocular microenvironment is both immunosuppressive and anti-inflammatory in nature. Pigment epithelial (PE) cells isolated from the eye possess the ability to suppress the T cell receptor-dependent activation of T cells and the induction of regulatory T cells in vitro. This property is dependent on the cells' capacity to produce cell-surface and soluble inhibitory molecules, for example CD86 (B7-2), transforming growth factor (TGF)-beta, thrombospondin-1, programmed cell death 1 ligand 1 (PD-L1/B7-H1), and cytotoxic T lymphocyte-associated antigen 2alpha. Cultured ocular PE cells from the iris, ciliary body, and retina can individually suppress T-cell activation via mechanisms that partially overlap. Moreover, PE-derived regulatory T cells acquire functions that play a role in establishing immune regulation in the eye. Multiple strategies are employed within the eye to control immune-mediated inflammation. This phenomenon is known as immune privilege and is instrumental in helping to prevent extensive damage to bystander cells that would otherwise lead to blindness. This review focuses on the immunosuppressive property and role of ocular PE cells in immune privileged sites.

Systemic levels of vascular endothelial growth factor before and after intravitreal injection of aflibercept or ranibizumab in patients with age‐related macular degeneration: a randomised, prospective trial

“…Systemic VEGF acts as a vascular protective factor by stimulating antiapoptotic-signalling pathways to enhance endothelial integrity and maintain the antithrombogenic and anti-inflammatory properties of the endothelium (Tsurumi et al 1997;Zachary et al 2000). Furthermore, VEGF blockade is known to decrease the extravasation of circulating lymphocytes, which were shown to express a receptor for this cytokine (Sugita 2009;Zhang et al 2010). Systemic immune-mediated processes might be altered by the inhibition of VEGF.…”

Expression and distribution of immunoglobulin G and its receptors in an immune privileged site: the eye

“…VjJj of the other clone showed high homology to that of cw9, with a mutation ratio of 2.16% and retina. The PE is the most important protective structure in ocular physiology, whereas it is also thought to contribute to the maintenance of the immune-privileged status of the eye [36]. Given the extensive expression of IgG and FccRs in the PE, it appears highly likely that endogenously produced IgG might play a protective role in this ''immune-privileged'' site.…”

Immunosuppressive Properties of Regulatory T Cells Generated by Incubation of Peripheral Blood Mononuclear Cells with Supernatants of Human RPE Cells

“…Normal mice were subcutaneously immunized in the neck region with 200 lg of interphotoreceptor retinoid-binding protein peptide (IRBP [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] emulsified in complete Freund's adjuvant (Difco, Detroit, MI) and containing Mycobacterium tuberculosis strain H37Ra (Difco). [22][23][24] Funduscopic examination was performed on days 14, 17, and 21 after immunization, and histologic examination was performed on day 21 after immunization.…”

“…For adoptive transfer experiments, GFP-labeled murine RPE-induced Tregs (1 3 10 6 cells) and control CD4 þ T cells (1 3 10 6 cells) were prepared. These T cells were injected intravenously (IV) into mice 14 days after immunization with IRBP [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] . After injection into mice with EAU, GFP-positive T cells were observed.…”

“…1,2 The immunoregulatory property of retinal PE (RPE) is related to intraocular suppression of immunogenic inflammation. Murine T cells have been converted into regulatory T cells (Tregs) by in vitro exposure to PE cells harvested from the retinas of uninflamed, healthy eyes.…”