The human thymus

Abstract

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 cell repertoire. Although the thymus has enormous regenerative capacity during fetal development, the regenerative capacity of the human postnatal thymus decreases over time. With the advent of intensive chemotherapy regimens for a variety of cancer syndromes, and the discovery that infection with the Human Immunodeficiency 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 with 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 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 normal life during the process of thymus involution. Thus, the human thymus can be thought of as a chimeric organ comprised of both central and peripheral lymphoid tissues. These observations have led us to postulate that the thymic epithelial atrophy and decrease in thymopoiesis that occurs in myasthenia gravis, HIV-I infection, and thymic involution may in part derive from cytokines or other factors produced by peripheral immune cells within the thymic perivascular space.

Measuring Recent Thymic Emigrants in Blood of Normal and HIV-1–Infected Individuals before and after Effective Therapy

“…Multiple lines of evidence indicate that HIV-1 infects thymocytes, not only in vitro but also in a SCID mouse implanted with human fetal thymus and liver (SCID-hu mouse) in vivo 123. Autopsy studies of HIV-1–infected individuals 4 or SIV-infected macaques 56 show both infection and altered histopathology of the thymus. Evaluation of thymic function in humans would be facilitated by noninvasive techniques to measure the output of thymocytes from this primary lymphoid organ.…”

“…These techniques, however, are not applicable to human studies. Computer tomography scan of the chest has been used to correlate thymic sizes of HIV-1–infected individuals to their CD4 + naive (CD45RA + CD62L + ) lymphocyte counts 10, but such an imaging technique cannot reliably measure the true lymphoid mass of the thymus 411.…”

Immunological Evaluation of Patients with Beta-Thalassemia major

“…In this study we investigated the thymic endocrine function, by evaluating a peptide hormone ‘thymulin’, secreted exclusively by thymic subcapsular and medullar cells [24], in order to improve our understanding of the immunological changes observed in patients with TM. The rosette inhibition assay by Dardenne and Bach [25]represents the unique assay available to evaluate the active form of the hormone, conjugated to zinc ion, as radioimmunological tests cannot discriminate between the biologically inactive form of the hormone not containing Zn (facteur thymique sérique, FTS) and thymulin (Zn-FTS) [26].…”

HIV-1 Infection of Human Thymic Stromal Cells and Thymocytes In Vitro

“…[4][5][6] Thymocyte maturation and selection is a sensitive, multifaceted process that can be disrupted by several infectious agents including HIV-1. [7][8][9] Although direct infection of thymocytes by HIV-1 may trigger cytopathology, this mechanism alone does not account for the profound loss of thymocytes seen during infection. 10 The capacity of HIV-1 to infect non-lymphoid cells, including thymic stromal cells, has been previously reported.…”