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November 18, 2002

Researchers study tolerance in ocular transplants

By Joy Bell

Unlike other parts of the body, the eye will tolerate the presence of foreign tissue in certain areas, such as the anterior chamber between the iris and the cornea, or the space underneath the retina. The same tissue placed elsewhere in the body (on the skin, for example) would trigger an immune reaction and be rejected.

School of Medicine researchers have studied this unique ability of the eye to develop methods of inhibiting rejection by selectively enhancing immunological unresponsiveness or “tolerance.” Yijun Xu and Judith Kapp of the departments of ophthalmology, pathology and the Winship Cancer Institute, reported the results of their work in the November issue of Investigative Ophthalmology and Visual Science.

The major problem with any organ or tissue transplantation is that the recipient usually rejects cells from another person (unless they are twins). The recipient’s immune system does not distinguish between a transplanted retinal cell, for example, or invading microorganisms such as bacteria and viruses.

Inflammation is the body’s way of fighting infection, as the white blood cells (called lymphocytes) and antibodies attack and destroy antigens carried by the “invader.” In the eye, inflammation may result in excessive tissue damage that could lead to blindness.
Xu and Kapp are studying how a phenomenon called Anterior Chamber-Associated Immune Deviation (ACAID) combats inflammation. ACAID occurs when the hypersensitivity of the eye against an invader is reduced with administration of an antigen, thereby decreasing the risk of sight-threatening inflammation.

Studies with mice have shown that by delivering a certain antigen, the white blood cells can be neutralized and their ability to produce antibodies reduced. Delivery of a soluble form of antigen into the anterior chamber of the eye of anesthetized mice triggered the ACAID phenomenon, decreasing the hypersensitivity in the eye and throughout the body.

The technique requires certain specific white blood cells, called gamma delta T cells, Xu and Kapp learned. In otherwise normal mice, which did not have a sufficient quantity of T cells, the immune response could not be inhibited. This led the Emory scientists to conclude that ocular tolerance depends upon the participation of these special lymphocytes.

Understanding how T cells affect tolerance may one day be used to prevent graft rejection and to provide novel treatments for patients with autoimmune diseases.