Background: The thymus undergoes age-related (physiological) involution in the course of normal ontogenetic development. In addition to this chronic involution, the thymus can also undergo an acute (age-independent) regression, defined as spontaneous, transient involution. This process is induced by either exogenous or endogenous factors, including some infections (infection-type involution). Objective: The purpose of the present work was to undertake a comparative study of the epithelial framework organization and cytokeratin immunoreactivity of human thymic epithelial cells during age-related and infection-induced involution. Methods: Routine methods for light and transmission electron microscopy, as well as indirect immunoperoxidase staining and immunogold electron microscopy, were applied. Results: The epithelial thymocyte microenvironment was of a generally similar cellular composition in both chronically and acutely involuted thymus. Structurally, aged thymus glands and infection-affected thymus glands displayed a large mass of adipose tissue containing scattered islands composed of epithelial cells, lymphocytes and reticular connective tissue. Correlation between thymus involution and regional peculiarities in the presence and distribution of cytokeratin-immunopositive cells and their intermediate filaments was investigated. Conclusion: The epithelial framework of the thymus undergoes reorganization during both age-related and infection-induced thymus involution. The involutionary processes demonstrated essential regional and intracellular (structural and immunocytochemical) differences. The epithelial cell rearrangement and cytokeratin modulation that we observed might be involved in thymic microenvironment plasticity and reorganization in the course of these processes.
The lysosomal membrane-associated glycoproteins LAMP-1 and LAMP-2 are the major constituents of lysosomal membranes with still undefined biological functions. As autophagy is an alternative model of programmed cell death in which lysosomes play a crucial role, we hypothesize that LAMPs might participate in this phenomenon in the involuting thymus. Thymic glands from cases with acute (infection induced) and chronic (senile) involution were examined immunohistochemically for the expression of LAMPs. In acute involution LAMP-1 was localized mainly in medullary epithelial cells, in single macrophages and lymphocytes. Hassall's corpuscules were stained less intensely as compared to control specimens. The quantitative analysis showed a significantly elevated LAMP-2 expression compared to LAMP-1. LAMPs were detected with very slight reactivity in the senile thymus. The enhanced expression of LAMPs, and mainly of LAMP-2, in epithelial cells of incidentally involuted thymus might be an indicator of acute cell injury requiring autophagic degradation of damaged structures. The diminished expression of LAMPs in age-involuted thymus could be a sign of the morphological reorganization and the functional disregulation of the gland. In conclusion, we present novel evidence for differential expression of LAMP-1 and LAMP-2 in thymic involution suggesting their possible involvement in the process of accidental involution of the thymic gland.
We have previously reported that the thymus of patients affected by myasthenia gravis (MG) is characterized by an elevated level of nerve growth factor (NGF), an endogenous polypeptide which plays a marked role in the cell biology of nervous and immune system. A consistent number of studies has shown altered expression of NGF in diseases associated with inflammatory and/or autoimmune responses. To evaluate the biochemical and molecular mechanisms implicated in NGF action in human myasthenic thymus, it is important to identify the cellular and structural organization of NGF receptors. To address this question, we investigated, both at light and electron microscopic levels, the cellular distribution of immunoreactivity for NGF and its low-affinity receptors, (p75) and its high-affinity receptor (TrkA) in the thymus of patients with MG. The present investigation shows that NGF and NGF receptors are overexpressed in the thymic cells of patients with MG compared to control subjects.
Several kinds of thymic cells express MHC class II antigens, including human-leukocyte-associated antigen-DR (HLA-DR) during postnatal development. The present study was focused on the detection and analysis of HLA-DR immunoreactivity in human fetal thymuses (6-7th month of gestation). Using monoclonal antibodies, indirect immunoperoxidase staining (IIP), immunogold electron microscopy (IGEM), enzyme-linked immunosorbent assay (ELISA) and flow cytometry, HLA-DR immunopositive (IP) thymic cells were found in samples studied. IIP and IGEM demonstrated the presence of HLA-DR IP stromal cells (SCs): epithelial cells (ECs), dendritic-like cells (DCs) and macrophages (MCs) as well as HLA-DR IP lymphocytes (Lys) in all thymic regions. HLA-DR immunoreactivity was more prominent in the medullary ECs (mECs) than in the cortical ECs (cECs). Strong staining of Hassall's corpuscles and the adjacent mECs was seen. The differences in the intracellular distribution of HLA-DR molecules were detailed by IGEM as a first attempt to analyse HLA-DR IP cells at ultrastructural level. ELISA data and two-colour flow cytometric analysis revealed the presence of HLA-DR IP and HLA-DR/CD3 double IP Lys in accordance with the immunocytochemical assays. The results presented enrich the information about HLA-DR IP components of the thymic microenvironment in developing human thymus and raise the question of their role during prenatal T cell differentiation and selection processes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.