Privileged Sites Accept Antigenic Mismatches

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In immunologically privileged sites, an allograft can be placed without engendering a rejection reaction. These sites include the anterior chamber of the eye, the cornea, the uterus, the testes, and the brain. The cheek pouch of the Syrian hamster is a privileged site used in experimental situations. Each of these sites is characterized by an absence of lymphatic vessels and in some cases by an absence of blood vessels as well. Consequently, the alloantigens of the graft are not able to sensitize the recipient's lymphocytes, and the graft has an increased likelihood of acceptance even when HLA antigens are not matched.

The privileged location of the cornea has allowed corneal transplants to be highly successful. The brain is an immu-nologically privileged site because the blood-brain barrier prevents the entry or exit of many molecules, including antibodies. The successful transplantation of allogeneic pancreatic islet cells into the thymus in a rat model of diabetes suggests that the thymus may also be an immunologically privileged site.

Immunologically privileged sites fail to induce an immune response because they are effectively sequestered from the cells of the immune system. This suggests the possibility of physically sequestering grafted cells. In one study, pancreatic islet cells were encapsulated in semipermeable membranes (fabricated from an acrylic copolymer) and then transplanted into diabetic mice. The islet cells survived and produced insulin. The transplanted cells were not rejected, because the recipient's immune cells could not penetrate the membrane. This novel transplant method enabled the diabetic mice to produce normal levels of insulin and may have application for treatment of human diabetics.

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