The Bay Area Reporter - December 12, 1995
Matthew Sharp and Dean Knutson - ACT UP/Golden Gate Writers Pool

The thymus is a small walnut-sized organ located above the heart. Scientists believe that it acts as a school for teaching T-cells their function. The organ is divided into two parts, the cortex and the medulla. The immature T-cells migrate from the bone marrow and enter the cortex of the thymus, where they become thymocytes.

Then a small percentage of thymocytes go into the medulla to continue the maturation process, and go into the bloodstream as immunocompetent "taught" T-cells. These are the T-cells that are hopefully restored in thymic transplantation.

As people mature the thymus becomes "involuted" (shriveled). This is possibly the reason the elderly have a reduced ability to fight infection. Studies have shown that adults over the age of 20 have difficulty refurbishing their immune systems that are destroyed after extensive radiation. Stress and HIV infection might also cause the architecture of the thymus gland to wear out; however, it is not clear how involved the thymus is in HIV disease.

Studies of autopsies in AIDS, as well as in other illnesses, have shown that the thymus is seriously damaged. However, autopsied thymuses may be shriveled simply from the trauma and stress of death.

The first experiments indicating a relationship between the thymus and immune function came from removing the thymus of newborn mice. These mice suffered from a lack of T-cells and an increase in infectious disease. Later, children with DiGeorge syndrome (a rare disorder of the thymus) were studied for answers on the function of the immune system without the thymus. Studies of thymic transplantation in this population have given us a model for possible transplants in HIV, and ideas for future research. Even though thymic transplantation worked in HIV-positive children with young thymus glands, it is not entirely clear, given the condition of the mature thymus, if the transplantation will work in adults with AIDS.

The March 1987 Archives of Internal Medicine: Vol. 147 included a study on thymus fragments transplanted into 15 people with AIDS. In eight of the patients, there was an increase in T8 cells, but not of T4 cells. This increase in T8 cells was associated with some clinical improvement. This study speculated that thymic transplants alone may not restore the immune system but should be studied as part of the strategy for immune reconstitution. Thymic transplantation is being revisited now with better technology.

The hope is that transplants in combination with stronger anti-retroviral treatments and other immune restoration techniques will allow one's body to regenerate its immune function.

From these studies, one could speculate that an increase in thymic activity, in addition to a boost of the body's production of thymocytes, may help one to restore immune function. Thymic transplants may be especially exciting to people with depleted T-cells, because if you are at an age where your thymus has naturally atrophied, there is concern that even if your body can produce more immature T-cells, if the thymus is not functioning, those thymocytes may not go through the maturation process necessary to make them immunocompetent.

Thymic transplantation was the focal point at the Project Inform Immune Restoration Think Tank in Houston, and most attendees agreed that the procedure was ready for further clinical study in adults. Community representatives from ACT UP/Golden Gate and Project Inform gave input into the protocol, and a few patients will receive the procedure this month. Immunologists Richard Hong, from the University of Vermont Genetics Lab, and John Dwyer from Prince of Wales Hospital in Sydney, Australia are the primary investigators.

Ethical and statistical considerations were debated at the Think Tank. Should the trial involve sixty people or thirty people with only two "healthier" arms? What viral load number should be allowed? Should IL-2 therapy also be administered? These and other questions were discussed at length, but will not delay the first transplants going ahead this month.

The operation is not a transplant as we like to think of transplants. Discarded thymic tissue is collected from children who have had surgery for congenital cardiac problems. (The surgery requires removal of part of the thymus.) The tissue is sliced micro-thin in a high tech Vegematic-like device. The slices are then prepared in culture for 10 to 14 days, and chemicals are added to kill pathogens that might be in the tissue.

A small incision is made in the abdominal wall where the thymus slices are grafted into the recipient. The recipient's thymus is not removed. The procedure is so simple that an overnight stay in the hospital is all that is needed.

The donor tissue is only partially genetically matched. Rejection of the thymus graft in people with AIDS is thought to be minimal; however, looking at rejection will be one of the aims of the study. Using partially matched tissue will enable more transplants to take place.

Advances in our knowledge of HIV pathogenesis, and better understanding of the immune system coupled with better anti-retrovirals and improved laboratory technology will enable thymic transplantation to move forward. The hope is that with this technology the immune system can be repaired for people with HIV.

ACT UP/Golden Gate meets every Tuesday at 7:30 at 592 Castro Street. Everyone is welcome.

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