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A protein in the eye may prevent immune response and protect eyes from disease

June 22, 2005

Scientists at The Schepens Eye Research Institute have discovered that a protein known as F4/80 found on immune cells in the eye and other parts of the body may have a function in the regulation of the body's immune response and protect delicate tissues that cannot survive the "inflammation" inherent in full-blown immunity.

"We believe that this discovery may ultimately help in the development of therapies for blinding eye diseases such as macular degeneration and autoimmune diseases that occur when the immune system goes awry," says Joan Stein-Sreilein, PhD, senior author of the study published in the May issue of the Journal of Experimental Medicine and senior scientist at The Schepens Eye Research Institute.

According to Stein-Streilein, the discovery is another piece of the "immune privilege" puzzle. Certain parts of the body, including the eyes, brain, gastrointestinal system and reproductive system have the ability to prevent the usual immune response onset when confronted with foreign invaders such as bacteria. Without this special reaction, the eye's delicate tissue would be destroyed by inflammation and the gastrointestinal tract could not tolerate the ingestion of food. The F4/80 molecule (also known as a glycoprotein) was first discovered two decades ago on immune cells in the eye, gut and other privileged sites, but its function has not been understood.

In an attempt to understand F4/80, Stein-Streilein and her team have been following the immune cells (also known as antigen presenting cells) containing the protein. In previous studies, the team found that when these F4/80 containing cells bring antigens (foreign substances) from the eye to the spleen, the spleen stimulates the production of what is known as a "regulatory" T cell which stops the immune response throughout the body as well as at the site where the invasion took place-in this case, the eye. In a full-blown immune response, other types of T Cells are stimulated that start the immune attack, inflammation, and tissue destruction.

Since the F4/80 protein was identified as a crucial player in the development of immune privilege, the Schepens' team postulated that the protein had an important role in immune regulation. In the current JEM study, the team investigated mice that did not produce F4/80. They found that the immune suppression did not occur when foreign substances were presented to the spleen by antigen presenting cells that did not have F4/80. "This led us to believe that the protein F4/80 had a direct role in stopping immune response," says Stein-Streilein.

Although the mechanism by which F4/80 stimulates the production of immune suppressing T Cells is unknown, the team believes that the protein may be involved in cell-cell communications.

The presence of F4/80 cells in other immune privileged sites, such as the brain and placenta, and its exclusion from T cell zones in the spleen suggests that F4/80 expression and immune activation may be mutually exclusive.

According to Stein-Streilein, the next steps for the group will be to tease out exactly how the protein accomplishes its goal. Ultimately knowledge of the F4/80 protein and its role in immune regulation may lead to novel therapies for autoimmune diseases of the eye and the body.

Schepens Eye Research Institute