Slipping past the immune centurions.

The cells of the immune system, like gallant warriors, protect the body from foreign invaders. Yet these cells appear to grant a special privilege to some tissues. Testes, eyes, and even the brain appear to slip quietly past the body's guardians.

These immune-privileged tissues can be transplanted from one individual to another without rejection, even among unrelated donors and recipients. Conversely, the immune system permits other tissues to be transplanted into these privileged sites.

Now, a study indicates that privileged tissues may not have been granted free rein by the immune system's lymphocytes after all. Instead, the tissues appear to produce a molecule, known as Fas ligand, that kills immune cells approaching with destructive intent. This finding could someday improve transplantation outcomes and mediate self-destructive autoimmune diseases.

"This is a highly specific immune suppression," says study author Richard C. Duke of the University of Colorado School of Medicine in Denver. "And if the cells [of a transplanted organ] express Fas ligand, it is protected from the immune system."

When lymphocytes become activated during an immune response, whether to a virus, bacterium, or transplanted organ, they manufacture a large number of molecules known as Fas and imbed them into their cell surfaces. When these Fas molecules encounter a Fas ligand on another lymphocyte, it triggers a process called apoptosis, which leads the Fas-carrying lymphocytes to commit suicide. Presumably, the interaction helps the immune system regulate itself, though scientists don't know how.

As it turns out, however, lymphocytes aren't the only tissues that produce Fas ligand. The Colorado group reports in the Oct. 19 Nature that the Sertoli cells found in the testes also produce large amounts of Fas ligand.

The researchers transplanted rat testes into the kidney capsule of unrelated rats and found that the transplants were not rejected. In order to demonstrate that the Fas ligand produced by Sertoli cells lends immune privilege to the testes, they transplanted the testes of a strain of mice that can't produce any Fas ligand into a normal rat. Without Fas ligand, the transplanted testes were aggressively rejected.

"We know now that Fas ligand is necessary to confer immune privilege," says Duke. "But we don't know yet that it is sufficient."

Nevertheless, Thomas A. Ferguson of the Washington University School of Medicine in St. Louis says that Duke's work "is really a nice story, and it explains a lot." Ferguson plans to publish similar results soon explaining immune privilege in the eye.

Duke has begun work on creating rats with pancreatic Fas ligands in order to see whether the organ will become immune-privileged when transplanted. The Fas ligands could also help combat autoimmune disorders such as rheumatoid arthritis, he suggests.