Alterations of the Thymus and Peripheral Lymphoid Tissues in Fatal Measles

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Measles Virus (MV) Nucleoprotein Binds to a Novel Cell Surface Receptor Distinct from FcγRII via Its C-Terminal Domain: Role in MV-Induced Immunosuppression

Laine

Trescol-Biémont

Longhi

et al. 2003

“…Measles virus infects epithelial cells and monocytes in the thymus (25,45), leading to a decrease in the size of the thymic cortex (10,44). Measles virus replication in human thymic epithelial cells in vitro results in terminal differentiation and apoptosis (39).…”

mentioning

confidence: 99%

Increased Thymic Output during Acute Measles Virus Infection

Permar¹,

Moss

Ryon³

et al. 2003

Measles virus infects thymic epithelia, induces a transient lymphopenia, and impairs cell-mediated immunity, but thymic function during measles has not been well characterized. Thirty Zambian children hospitalized with measles were studied at entry, hospital discharge, and at 1-month follow-up and compared to 17 healthy children. During hospitalization, percentages of naïve (CD62L ؉ , CD45RA ؉ ) CD4 ؉ and CD8 ؉ T lymphocytes decreased (P ‫؍‬ 0.01 for both), and activated (HLA-DR ؉ , CD25 ؉ , or CD69 ؉ ) CD4 ؉ and CD8 ؉ T lymphocytes increased (P ‫؍‬ 0.02 and 0.03, respectively). T-cell receptor rearrangement excision circles (TRECs) in measles patients were increased in CD8؉ T cells at entry compared to levels at hospital discharge (P ‫؍‬ 0.02) and follow-up (P ‫؍‬ 0.04). In CD4 ؉ T cells, the increase in TRECS occurred later but was more sustained. At discharge, TRECs in CD4 ؉ T cells (P ‫؍‬ 0.05) and circulating levels of interleukin-7 (P ‫؍‬ 0.007) were increased compared to control values and remained elevated for 1 month, similar to observations in two measles virus-infected rhesus monkeys. These findings suggest that a decrease in thymic output is not the cause of the lymphopenia and depressed cellular immunity associated with measles.

“…Autopsies of patients with fatal measles infections demonstrated degenerative and/or necrotic lesions in the thymus associated with a rapid and predominant loss of the thymic cortex (38). A marked involution of the thymic medulla was also observed, and MV antigens were found in Hassal's corpuscules (11,38). We previously demonstrated that, in vitro, MV replication profoundly affects human cortical TEC biology (37).…”

mentioning

confidence: 92%

“…MV initially replicates in the respiratory tract and then spreads to local lymphoid tissue, where virus replication can occur in macrophages and/or dendritic cells. This secondary viremia allows the spreading of the virus to other lymphoid organs, including the thymus (11,27,38). Autopsies of patients with fatal measles infections demonstrated degenerative and/or necrotic lesions in the thymus associated with a rapid and predominant loss of the thymic cortex (38).…”

mentioning

confidence: 99%

Interferons Mediate Terminal Differentiation of Human Cortical Thymic Epithelial Cells

Vidalain

Laine

Zaffran

et al. 2002

In the thymus, epithelial cells comprise a heterogeneous population required for the generation of functional T lymphocytes, suggesting that thymic epithelium disruption by viruses may compromise T-cell lymphopoiesis in this organ. In a previous report, we demonstrated that in vitro, measles virus induced differentiation of cortical thymic epithelial cells as characterized by (i) cell growth arrest, (ii) morphological and phenotypic changes, and (iii) apoptotis as a final step of this process. In the present report, we have analyzed the mechanisms involved. First, measles virus-induced differentiation of thymic epithelial cells is shown to be strictly dependent on beta interferon (IFN-␤) secretion. In addition, transfection with double-stranded RNA, a common intermediate of replication for a broad spectrum of viruses, is reported to similarly mediate thymic epithelial cell differentiation through IFN-␤ induction. Finally, we demonstrated that recombinant IFN-␣, IFN-␤, or IFN-␥ was sufficient to induce differentiation and apoptosis of uninfected thymic epithelial cells. These observations suggested that interferon secretion by either infected cells or activated leukocytes, such as plasmacytoid dendritic cells or lymphocytes, may induce thymic epithelium disruption in a pathological context. Thus, we have identified a new mechanism that may contribute to thymic atrophy and altered T-cell lymphopoiesis associated with many infections.The thymus is a primary lymphoid organ that ensures Tlymphocyte differentiation from bone marrow-derived progenitors (for reviews, see references 3 and 21). Thymic microenvironments are composed of a network of thymic epithelial cells (TEC), present in both the cortex and the medulla, and hematopoietic cells such as macrophages and dendritic cells. Thymocytes migrate, while differentiating, through distinct microenvironments in the subcapsular cortex, the deep cortex, the cortico-medullary junction, and the medulla, where they are finally released, as mature T cells, into the bloodstream. Thymic microenvironments sustain thymocyte development, providing survival, proliferation, and differentiation signals that allow T-cell receptor gene rearrangements. Moreover, interaction of immature T cells with thymic microenvironments ensures the production of major histocompatibility complex-restricted, self-tolerant T cells. Within the cortex, positive selection of immature T cells expressing functional T-cell receptor is mediated mainly by cortical TEC, whereas in the medulla, negative selection of developing autoreactive T cells is ensured by antigen-presenting cells of hematopoietic origin and, to a lesser extent, the TEC subset. Thus, thymic microenvironments support thymocyte survival and differentiation into mature T cells.Among the factors that profoundly affect T-cell lymphopoiesis is infection by measles virus (MV), a single-stranded RNA (ssRNA) virus from the Paramyxoviridae family that induces a severe lymphopenia and immunosuppression in humans (16). MV initially replicates in the re...