An aged thymus undergoes rejuvenation when transplanted into a juvenile animal and induces tolerance to organ transplants from the same donor, according to a study by Shuji Nobori, a postdoctoral fellow, and Kazuhiko Yamada, an HMS associate professor of surgery in the Transplantation Biology Research Center at Massachusetts General Hospital. The study was published Dec. 12 in Proceedings of the National Academy of Sciences.
The researchers carried out the transplantation experiments in miniature swine that bear immunological and physiological similarities to humans. When four-month-old animals were transplanted with vascularized thymic lobes from 20-month-old animals, the thymuses underwent structural and functional renewal, causing them to resemble their counterparts from young animals. When the experimental animals underwent a renal transplant after the vascularized thymic grafts were rejuvenated, they accepted the donor-matched grafts without further immunosuppression, indicating tolerance had been induced. The researchers observed these effects across differing levels of major histocompatibility complex (MHC) incompatibility. The vascularization of the thymic lobes prior to transplantation ensured immediate reversion to function inside the host animal.
An important observation of this study is that thymic rejuvenation is dependent on external stimuli within the host animal and not on the local environment within thymic tissue. In an effort to extend this finding, the researchers are involved in elucidating the stimuli from the host environment that induce rejuvenation.
The thymus has a central role in teaching thymocytes to differentiate between self- and nonself-antigens. The organ presents a vast repertoire of antigens to the immature cells, which arrive from the bone marrow. Through positive selection, T cells that recognize nonself-antigens continue to mature and pass into peripheral circulation; those that react with self-antigens are deleted through negative selection. Yamada explains that recognition of donor antigens as self-antigens within the thymus may facilitate their subsequent acceptance by host T cells, ensuring survival of the transplant.
This study suggests advantages over current methods of transplantation. Patients who now receive organ transplants need to be on immunosuppressive drugs for life. But transplantation of the donor thymus prior to the organ transplant may obviate this need. Furthermore, xenogeneic transplants, which traditionally are harder for the recipient to accept than allogeneic procedures, may also be more easily accepted if accompanied by thymic transplants from the donor animals. This would also circumvent the shortage of transplant organs from humans.
