>Contents>Ocular Immune Privilege
Until very recently, the notion that privilege directed at innate immunity exists was not seriously considered. However, within the past few years, reports from several laboratories have produced irrefutable evidence that the ability of the innate immune system to express itself in the eye is impaired and modified. Perhaps the most dramatic example comes from the laboratory of Dr. J.Y. Niederkorn where work was carried out with a mouse tumor cell line that is susceptible to lysis by NK cells. When this tumor cell line was injected into the flank of mice with a severe deficit in adaptive immunity, the tumor was rejected – because these mice still possess an intact innate immune system. This tumor rejection was shown to be mediated by NK cells. When these same tumor cells were injected into the anterior chamber of the eye of adaptive immunodeficient mice, no rejection occurred. Instead, the injected cells formed progressively growing tumors. This result formally demonstrates the existence of innate immune privilege in the eye.
It is of interest that the tissues within the eye display considerable vulnerability to the deleterious effects of effectors of innate immunity. Corneal endothelial cells express very low levels of MHC class I molecules; NK cells are particularly equipped to recognize and kill cells with low class I MHC expression. Thus, corneal endothelium is vulnerable to lysis by NK cells. Corneal endothelial cells also express CD14, the receptor for the LPS-binding protein. This receptor targets LPS to the endothelium, thereby inviting LPS to recruit inflammatory cells that could harm this delicate, crucial inner layer of the cornea. The corneal endothelium is exquisitely sensitive to reactive oxygen intermediates and nitric oxide (NO), and these toxic molecules are the products of LPS-activated macrophages and neutrophils. Most ocular parenchymal cells express CD95 ligand constitutively. Reciprocally, neutrophils constitutively express CD95, and when neutrophils interact with CD95 ligand-bearing cells, the neutrophils are triggered to release pro-inflammatory mediators and destructive hydrolytic enzymes. Since these mediators additionally attract neutrophils and macrophages, and since both cells quickly release TNF-alpha when activated, the high level of expression of receptors for TNF-alpha on ocular cells renders these cells vulnerable to the deleterious consequences of this powerful, pleiotropic cytokine. It is a small wonder that the eye has acquired a protective adaptation that enables it to blunt the harmful effects of innate immunity.
The Eye's Dilemma
Immune Privilege
Anterior Chamber of the Eye as an Immune- Privileged Site
Inflammation of Relation to Innate and Adaptive Immune Responses
Ocular Factors That Promote Immune Tolerance of Eye-Derived Antigens
Factors That Modify Expression of Ocular Adaptive Immunity
Innate Immune Privilege in the Eye
Factors That Modify Expression of Innate Ocular Immunity
Clinical Meaning of Ocular Immune Privilege
Selected Reading
Biography
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