The human thymus - A chimeric organ comprised of central and peripheral lymphoid components (vol 18, pg 61, 1998)

The human thymus is a lymphoepithelial organ in which T cells develop durin g fetal life. After maturation and selection in the fetal thymic microenvir onment, T cells emigrate to peripheral lymphoid tissues such as the spleen, gut, and lymph nodes, and establish the peripheral T cell repertoire. Alth ough the thymus has enormous regenerative capacity during fetal development , the regenerative capacity of the human postnatal thymus decreases over ti me. With the advent of intensive chemotherapy regimens for a variety of can cer syndromes, and the discovery that infection with the Human Immunodefici ency Virus (HIV) leads to severe 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. During a recent study of the thymus in HIV infection, we observed many CD8(+) T cells in AIDS thymuses that had markers consistent w ith those of mature effector cytotoxic T cells usually found in peripheral immune tissues, and noted these CD8(+) effector T cells were predominately located in a thymic zone termed the thymic perivascular space. This article reviews our own work on the thymus in HIV-1 infection, and discusses the w ork of others that, taken together, suggest that the thymus contains periph eral immune cell components not only in the setting of HIV infection, but a lso in myasthenia gravis, as well as throughout normal life during the proc ess of thymus involution. Thus, the human thymus can be thought of as a chi meric organ comprised of both central and peripheral lymphoid tissues. Thes e observations have led us to postulate that the thymic epithelial atrophy and decrease in thymopoiesis that occurs in myasthenia gravis, HIV-1 infect ion, and thymic involution may in part derive from cytokines or other facto rs produced by peripheral immune cells within the thymic perivascular space .