Tricking the Immune System
Insulin-dependent diabetes mellitus afflicts more than a million North Americans. It's long been one of those aggravating illnesses that can be treated but not cured; once the disease progresses to the point that its victims need insulin injections to stay alive, they'll need that additional insulin for the rest of their lives.
In some ways, its cause is well understood. In a healthy person, clusters of specialized cells---islet cells---in the pancreas gland manufacture insulin, a protein hormone essential for metabolizing carbohydrates. In a person with diabetes, these islet cells degenerate and die, no longer providing the necessary insulin.
Once it became technologically possible, medical researchers tried transplanting functioning islet cells into the pancreas glands of diabetics to cure their disease. In theory, that was a logical treatment, but in practice it didn't work so well.
Over eons of evolution, we have developed immune systems that discriminate between self and not-self---and wipe out the not-self intruders. This is what makes organ transplants such a challenge: the immune system works against strange heart, kidney, or islet cells as well as bacterial cells. Thus transplant recipients' immune systems quickly attacked the new islets, unless those patients also received immuno-suppressant drugs. Just as the name implies, these drugs suppress the action of the immune system. They're strong medicine, and they have undesirable side effects (including leaving the recipient vulnerable to the array of invading disease organisms people encounter every day). If a patient will die without a heart transplant, he or she may well think the risk of taking immuno-suppressants is worth it, but diabetics can fall back on insulin injections. For them, this cure might well be worse than the disease.
For medical researchers, suspecting they have a cure but not being able to apply it is a frustrating situation. Dr. Ali Naji of the University of Pennsylvania thinks he may have found a way around that frustration, and he has cages of healthy rats to support his contention.
The rats once had diabetes. Naji cured them with transplanted islet cells, but he didn't install the new cells in the rodents' pancreas glands. Instead, each rat received the cells into a different gland, the thymus. It was a matter of good judgment, not bad aim. Naji reasoned that the thymus would offer special advantages because it is the nurturing ground for some key cells of the immune system, T lymphocytes.
At first glance that would seem the worst place to put a transplant--like putting a chicken in a fox den. The T lymphocytes growing in the thymus are killer cells that seek out and destroy substances bearing antigens to which they respond, which certainly includes not-self islet cells. But Naji understood that T cells develop their chemical sensitivities while they mature. Rather like children, they learn to identify who is a member of the family and who isn't while they're growing up. He gave the experimental rats one shot of a heavy-duty immunosuppressant to wipe out 90 percent of the full-grown T cells so that a new crop of young T cells could mature in the company of the implanted islet cells. It worked. The islet cells "resist rejection," as Naji put it in the recent issue of Science magazine where his work is reported. The rats' killer T cells ignored the implanted islet cells, which are functioning well in their odd new home.
The experiment is only a first step on a long road; the technique will be tested on larger animals next, perhaps pigs or dogs. It will be years before human experiments can take place.
When they do, diabetics may not be the first subjects. After the initial transplants of islet cells, Naji and his colleagues tried moving kidney tissue from the original islet-cell donor rats into the kidneys of the rats that had received the islet cells. The transplanted kidney cells were not attacked. Somehow, after accepting the new islet cells, the T lymphocytes extended recognition to cells from other tissues. This opens a new avenue in organ transplant research, one that might eventually do away with the need for immunosuppressant drugs entirely.
