Immunological senescence and thymic function in transplantation

In the field of organ transplantation, the state of thymic function has not been a major concern but data from bone marrow transplantation studies have unravel the persistence of some thymopoiesis in the adult and, more importantly, the possibility of reinducing it. Given the central role of the thymus in tolerance, these facts have stimulated the interest in the biology of the thymus in humans. Contemporarily, basic research has provided new tools, if imperfect, to monitor thymic function, that is, T-cell receptor excision circles, markers for lymphocytes recently emigrated from the thymus and new imaging techniques. The deployment of these new tools is already changing some paradigms and has now established that re-enactment of thymic activity in the course of bone marrow transplantation or in patients with human immunodeficiency virus on highly active anti-retroviral therapy is beneficial and that can be achieved in the adult. Clinical trials using thymopoiesis-stimulating factors are underway. On the other hand, the discovery that the thymus contains a broad representation of self-antigens and that this depends on the expression of the product of the gene AIRE by the medullary thymic epithelial cells opens the possibility of manipulating central tolerance. Current protocols inducing microchimerism to generate tolerance to solid organ grafts suggest that this could be a feasible therapeutic goal. Therefore, there are many signs indicating that a period of translational research applying the principles of thymic biology and central tolerance to transplantation has already started.