Fighting AIDS on the Body's Own Ground

Researchers are stunned by a gland they thought dormant

After years of research on hundreds of San Franciscans, a University of California, San Francisco doctor has discovered one of the human immune system's best-kept secrets.

Dr. Joseph Michael McCune, associate professor of medicine at UCSF, and an associate investigator at the university's Gladstone Institute of Virology and Immunology at San Francisco General Hospital, led a recent study that unexpectedly found thymus tissue in adults infected with HIV. This discovery could change the way doctors treat some AIDS patients.

The thymus is an organ located behind the breastbone that makes T cells -- in fact, it puts the "T" in "T cell." Normally, its work takes place before birth and during the growing years. After puberty, the thymus typically fills with fatty tissue and becomes dormant. But by then, most people have all the T cells they need -- unless those cells are destroyed.

HIV destroys T cells. And previous studies have indicated that the virus can also infect and destroy thymus tissue. However, a few years ago, patients began to show increases in T cells in response to drug cocktails and other therapies. The mystery was where those T cells were coming from.

In 1995, McCune and his team of researchers began to study HIV-infected and healthy adults in search of the answer. Their project was funded by grants from the National Institutes of Health, the Pediatric AIDS Foundation, and the Center for AIDS Research at UCSF. And their subjects -- more than 200 people -- were enlisted by Project Inform and ACT UP Golden Gate.

"It would never have been possible to do this [study] without the help of these organizations," McCune says. "They recruited the patients, they got people to the hospital, and they got blood from them. Project Inform and ACT UP Golden Gate actually drove to these people's houses and got their blood samples."

The study yielded a rare result in modern science: an outcome not predicted by any textbook or clinical experience. The biggest surprise, of course, was that McCune and his team found thymus tissue in HIV-infected adults. In adults older than 40, the difference was particularly dramatic. Thymus was present in five out of 10 HIV patients older than 40, while there was no trace of thymus at all in their healthy counterparts.

The most exciting theory here, says McCune, is that the bodies of some HIV-positive patients have somehow reactivated their thymuses in response to a low T cell count, or some other reaction. This theory appears more likely when you consider that other parts of the body work the same way. For instance, in anemic patients, elements launched from the kidneys "tell" the bone marrow to start producing red blood cells because those cells are in short supply.

"All biological systems have feedback which fine-tunes the system," says McCune. "[The thymus] is obviously reacting to something."

Of course, unlocking one mystery leads to several more. One of the continuing studies McCune and his colleagues have launched focuses on developing a better test for thymus. The method used for his previous research -- a combination of radiology and antibody tests -- is expensive and complicated.

A flurry of other studies, likely to include invasive procedures to actually remove thymus tissue and test it, are sure to follow. All of this now leads to the next big questions: How do you turn the thymus back on? And can doctors learn to "instruct" a patient's body to replace destroyed T cells?

The most immediate impact of McCune's work is likely to be seen in measuring the effects of drug cocktails and immune system therapies. At the very least, researchers now know that a patient may have thymus and, therefore, the ability to produce T cells, which may help explain why some patients respond better to certain drugs than do others. To be more effective, those patients would likely be treated differently than patients with no thymus present. In other words -- one plan of action no longer needs to fit everyone.

 
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