Cells Covering the Iris Stops Damaging Immune Inflammation

Newswise — Scientists at Schepens Eye Research have found that the iris pigment epithelium (IPE), a thin layer of cells lining the iris of the eye, produces a molecule that disables T Cells, the cells that normally attack and kill foreign microbes invading the body. The results, published in the current (July 7) Journal of Experimental Medicine, are the first to explain the mechanism by which the iris protects the eye from inflammatory immune responses, which, though well-intended by the immune system, can cause blindness. The discovery, the authors believe, will ultimately lead to therapies for diseases such as uveitis, herpes and viral eye infections that affect millions worldwide and are caused by an unchecked immune response in the eye.

"This is an important breakthrough in our understanding of the eye's immune privileged state, which when functioning well protects our vision, but when it fails, is unable to stop immune inflammation from destroying vision," says J. Wayne Streilein, MD, senior author of the study, senior scientist at Schepens Eye Research Institute, and Professor of Ophthalmology at Harvard Medical School..

The eye, the brain, and the reproductive system are all known to be "žimmune privileged. This means that they are able to be protected by immunity without suffering the ravages of inflammation that often accompany immune elimination of foreign microbes. Inflammation, which is the usual way the body defends itself, can also harm irreplaceable normal tissues of the organs it is trying to defend. Because it cannot regenerate itself, the eye needs to be immune privileged since any inflammation, even if well intended by the immune system, can damage delicate tissue and cause permanent vision loss, Scientists, many of whom are at Schepens Eye Research Institute, are unraveling the mysteries of immune privilege and finding that individual parts of the eye know how to stop T Cells in ways that avoid inflammation. Although scientists have known for 20 years that iris PE cells can inhibit T Cells, the mechanism has been unknown.

The iris is the colored center of the eye that prevents too much light from entering and regulates the size of the pupil to accommodate vision over short and long distances. The iris is very vascular, which means it is prime site for T Cells to enter the eye through the blood stream.

To get a better understanding of the immune privileged mechanisms of the iris, Streilein and co-investigator Sunao Sugita, M.D., Ph.D., put IPE cells from normal mice in a culture with pure T Cells. They compared IPE with pigment epithelium from other parts of the eye (the ciliary body and the retina). They found that all pigment epithelia suppressed the T Cells, but that iris pigment epithelium alone used a molecule known as CD86 to stop T cells. CD86 is normally used by cells of the immune system to stimulate T cells, but CD86 on iris PE has the opposite effect. Streilein and Sugita then discovered that CD86 binds to a molecule called CTLA-4 on T cells, and it is this molecule that turned the T cells off.

The researchers concluded that iris PE cells achieve immune privilege by high-jacking CD86 from the immune system, and then using this molecule to fool T cells into submission.

Says Streilein, "When inflammation does occur in the iris, as in the case of uveitis, an eye inflammation that impacts almost a million people in the US alone, we suspect that immune privilege in the eye has failed. From this study, we now have a foundation for developing new therapies to restore immune privilege in this part of the eye, and thereby prevent vision loss from inflammation."

The next steps for Streilein and his team include finding the mechanisms that enable other eye tissues to create immune privilege, and using this knowledge to devise treatments to prevent inflammation and loss of sight.

The JEM study, "Iris pigment epithelium expressing CD 86 (B7-2) directly suppresses T cell activation in vitro via binding to cytotoxic T-lymphocyte associated Antigen 4 can be found online at http://www.jem.org/current.shtml#ARTICLE.

Schepens Eye Research Institute. Located in Boston, Massachusetts is an affiliate of Harvard Medical School and the largest independent eye research institute in the world.