( ivated inhibitory receptors down-regula...)Natural Approach to Immune Regulation May Help Transplant Patients,Health

ivated 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 Dr. 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. Unfortunately, he notes, cancer and some viruses seem capable of similar manipulation.

Using this approach, he has been able to prolong acceptance of skin grafts, which are typically rapidly rejected, sometimes indefinitely.

He's also getting T cells, another major player in the immune response, to express inhibitory receptors. Normally dendritic cells show an invader to T cells which produce cytotoxic T cells to destroy it. But when T cells express the inhibitory receptor, they go silent and may even die.

A long list of other cells that provoke an immune response might be "kept under control" by this approach, Dr. Horuzsko says.

He envisions, in the not too distant future, giving cytokines and growth factors to patients so targeted cells will express inhibitory receptors then delivering a sort of HLA-G manufacturing plant, probably blood-derived stem cells modified to produce it. In patients who already express inhibitory receptors, it may be enough to give only HLA-G. Dr. Horuzsko plans to further investigate this expression that occurs soon after an organ transplant in some patients.

These natural approaches would be used to prepare a patient for transplant and activated when problems with rejection emerge.

"I believe this natural mechanism is a very powerful tool for protecting tissue a
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