THE HUMAN THYMUS - A CHIMERIC ORGAN COMPRISED OF CENTRAL AND PERIPHERAL LYMPHOID COMPONENTS

The human thymus is a lymphoepithelial organ in which T cells develop during fetal life. After maturation and selection in the fetal thymic microenvironment, T cells emigrate to peripheral lymphoid tissues such as the spleen, gut, and lymph nodes, and establish the peripheral T c ell repertoire. Although the thymus has enormous regenerative capacity during fetal development, the regenerative capacity of the human post natal thymus decreases over time. With the advent of intensive chemoth erapy regimens for a variety of cancer syndromes, and the discovery th at infection with the Human Immunodeficiency Virus (HIV) leads to seve re loss of CD4(+) T cells, has come the need to understand the role of the human thymus in reconstitution of the immune system in adults. Du ring a recent study of the thymus in HIV infection, we observed many C D8(+) T cells in AIDS thymuses that had markers consistent with those of mature effector cytotoxic T cells usually found in peripheral immun e tissues, and noted these CD8(+) effector T cells were predominately located in a thymic zone termed the thymic perivascular space. This ar ticle reviews our own work on the thymus in HIV-1 infection, and discu sses the work of others that, taken together, suggest that the thymus contains peripheral immune cell components not only in the setting of HIV infection, but also in myasthenia gravis, as well as throughout no rmal life during the process of thymus involution. Thus, the human thy mus can be thought of as a chimeric organ comprised of both central an d peripheral lymphoid tissues. These observations have led us to postu late that the thymic epithelial atrophy and decrease in thymopoiesis t hat occurs in myasthenia gravis, HIV-1 infection, and thymic involutio n may in part derive from cytokines or other factors produced by perip heral immune cells within the thymic perivascular space.