Abstract
Evidence of immune privilege in the eye was recorded almost 140 years ago, yet interest in immune privilege languished for almost a century. However, the past 35 years have witnessed a plethora of research and a rekindled interest in the mechanisms responsible for immune privilege in the anterior chamber of the eye. This research has demonstrated that multiple anatomical, structural, physiological, and immunoregulatory processes contribute to immune privilege and remind us of the enormous complexity of this phenomenon. It is widely accepted that immune privilege is an adaptation for reducing the risk of immune-mediated inflammation in organs such as the eye and brain whose tissues have a limited capacity to regenerate. Recent findings suggest that immune privilege also occurs in sites where stem cells reside and raise the possibility that immune privilege is also designed to prevent the unwitting elimination of stem cells by immune-mediated inflammation at these sites. Uveal melanoma arises within the eye and as such, benefits from ocular immune privilege. A significant body of research reveals an intriguing parallel between the mechanisms that contribute to immune privilege in the eye and those strategies used by uveal melanoma cells to evade immune elimination once they have disseminated from the eye and establish metastatic foci in the liver. Uveal melanoma metastases seem to have “plagiarized” the blueprints used for ocular immune privilege to create “ad hoc immune privileged sites” in the liver.
Highlights
The roots of immune privilege reach back two centuries to an observation made by the Dutch ophthalmologist van Dooremaal (1873)
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family and is expressed on cells lining the interior of the eye and is believed to contribute to ocular immune privilege in a manner similar to that invoked by PD-L1 (Lee et al, 2002; Wang et al, 2003)
What was originally perceived as an anatomical anomaly in which the putative absence of lymphatic channels in the eye and brain acted to sequester antigens and create a state of immunological ignorance has evolved into a more complex and dynamic phenomenon that is the sum total of processes and molecules that prevent the induction and expression of both innate and adaptive immunity
Summary
The roots of immune privilege reach back two centuries to an observation made by the Dutch ophthalmologist van Dooremaal (1873). It is noteworthy that non-classical class Ib molecules are expressed in the testis (Slukvin et al, 1999; Ryan et al, 2002) and in the placenta (Kovats et al, 1990; Ishitani and Geraghty, 1992; Rouas-Freiss et al, 1997, 1999) Both soluble and cell membrane-bound molecules that inhibit innate immune responses are expressed in both the eye and in sites where stem cells reside (Table 1). Many of the strategies employed to buffer injurious innate immune responses in the eye and in sites of stem cell residence are effective in blocking adaptive immune responses that have the potential to damage stem cells and ocular tissues that cannot regenerate. ANTI-INFLAMMATORY AND IMMUNOSUPPRESSIVE FACTORS The AH contains at least five factors that inhibit the expression of T cell-mediated inflammation: (a) TGF-β; (b) α-melanocyte stimulating hormone (α-MSH); (c) vasoactive intestinal peptide (VIP); Frontiers in Immunology | Immunological Tolerance
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