Human leukocyte antigen G, or HLA-G, is a member of a gene family called major histocompatibility complex that provokes an immune response, says Dr. Anatolij Horuzsko, reproductive immunologist at the Medical College of Georgia.

The placenta expresses HLA-G from the earliest stages of embryo implantation and the molecule goes away toward the end of pregnancy. Growth factors and cytokines bring to the surface inhibitory receptors previously buried inside immune cells so they can interact with the HLA-G.

Amazingly, scientists have documented this natural immunosuppression, to a lesser extent, in at least one more situation: when an organ is transplanted. Horuzsko wants to augment this natural process so transplant patients won’t require a lifetime of generalised immune suppression that puts them at risk for many other diseases.

He has created animal models in which these inhibitory receptors are expressed on the cell surface. Using the same mixture the body uses he also gets the receptors expressed on the surface of human cells in a test tube. He gives HLA-G in both situations and studies the response. In dendritic cells, major orchestrators of the immune response, he has watched how activated inhibitory receptors down-regulate the function of stimulators of the immune response also present on the cell surface. Interestingly, the targets are members of the major histocompatibility complex family to which HLA-G belongs.

“These dendritic cells are not defective, but they develop tolerogenic properties, which are not normal for them,” says Horuzsko, who equates modifying the immune response to turning down the volume of a television. “We think we can help them into a tolerogenic pathway by giving HLA-G and get them to ignore the antigen coming from transplanted tissue,” he says. Using this approach, Horuzsko has been able to prolong acceptance of skin grafts, which are typically rapidly rejected, sometimes indefinitely.; Source: Medical College of Georgia