Ultrastructural study of thymic microenvironment involution in aging mice.

Aging involves morphological alterations of the thymus and deregulation of various immune response parameters. Altogether, these phenomena have been termed thymic involution. Using electron microscopy, we studied the morphological ultrastructure of the thymic microenvironment in aged mice. We observed cellular damages which progressively affected all the thymic stroma. At later stages (i.e., about 18-20 months old), a disappearance of the organ architecture with a drastic decrease in lymphocyte number was observed. The loss of cellular integrity of the microenvironment with lysis of cellular membranes and formation of a large and clear cytoplasmic layer engulfing a few remaining lymphocytes was noted. Extensive lipidic invasion surrounding the remaining epithelial cells grouped in nest formations and/or bordering cytics cavities was also present in these thymus from aged mice. Because the thymic microenvironment plays an important role in the "education" and functional maintenance of T cells and because the alteration of this cellular entity precedes a decline in certain immune functions, it can be suggested that membrane alterations, lack of cellular microenvironment integrity, and T cell dysfunction are correlated.

Thymic reticulum of mice. III. The connective compartment (innervation, vascularisation, fibrous tissues and myoid cells).

T lymphocytes interact at various levels of differentiation, with cells of the thymic reticulum, forming a peculiar and complex microenvironment. Following earlier descriptions by electron microscopy of three types of epithelial cells and two types of non-epithelial cells (macrophages and interdigitated cells) forming the thymic microenvironment, we report a study on a third compartment, the connective tissue, whose elements occur throughout the organ. The components of the capsule and trabeculae, the vascularisation and the innervation of the thymus and the presence of a few myoid cells are described. This is very rarely studied in ultrastructure. All these cells are completely imbricated and form a network trapping the lymphocytes, playing an essential role in the differentiation, maturation and selection of T cells.

Ultrastructural studies of mouse thymic reticulum. II. Non-epithelial component.

In this study we describe two types of non-epithelial cells forming a part of the thymic reticulum: macrophages with high phagocytic function, present in the cortex and medulla of the organ, and interdigitated cells present at the corticomedullary junction and in the medulla. These cells, in relation with epithelial cells, form a meshwork, a thymic microenvironment which influences the differentiation and maturation of T lymphocytes. These non-epithelial cells were probably mobile and their precursors exist in bone marrow. It has not yet been determined whether they are both of the same lineage and whether there is or is not common lineage between macrophages and interdigitated cells. Their role as accessory cells in the immune response seems evident. We will compare our observations with those of other authors. We will also discuss several issues concerning these two cell types; their nomenclature, their interrelationship in the thymic reticulum, their function, and their relationship to other similar cells in situ and to cells isolated in vitro, which perhaps are similar.

Pattern of secretion in thymic epithelial cells: ultrastructural studies of the effect of blockage at various levels.

The observation of secretory phenomena in mouse thymic epithelial cells is disappointing since no real secretion image is found. An adequate technique for such a study is to block the secretion pathway and to observe by electron microscopy cells accumulating secretory products. For this purpose, we used three means of blocking secretion: Firstly, since the thymic epithelial cell is regulated by a feedback phenomenon, secretion was blocked by antibodies against thymulin, one of the hormones secreted by these cells. Secondly, colchicine was used to modify the intracellular transport of the secretory product. In both of these types of experiments, electron microscopy showed a great increase in the number of "clear vacuoles" and their granular contents in epithelial cells. In a third series of experiments, we used monensin at a concentration that blocks the intracellular transport of secretory proteins at the various levels of the Golgi apparatus. In this series, only an increased number of vacuoles was observed, but they appeared devoid of all granular content. It can be concluded that in the thymic epithelial cell, a discrete system of secretion directs the passage of the product, originating in the cisternae of the endoplasmic reticulum, into "clear vacuoles", the terminal element of the cellular secretory apparatus.

Thymic reticulum of autoimmune mice. I. Ultrastructural studies of the diabetic (db/db) mouse thymus.

The thymus of the db/db mouse, an autoimmune strain with insulin-dependent diabetes mellitus and manifesting hyperglycemia, polyuria, glycosuria and obesity, was observed by electron microscopy. Its comparison with normal thymuses and thymuses from non-diabetic obese mice has revealed two major differences: first, the presence of crystal-like structures in some of the numerous clear vacuoles in cells, and second, a modification of the cells forming the border of cystic cavities. These cells contain two types of granules which are quite plentiful. One variety is clear and big, and a second type is small and dense, with an aspect similar to that of secretion granules. It is hypothesized that the crystalloid formations found in epithelial cells, and the presence of small, dense granulations in cells bordering the cystic cavities, are a consequence of the abnormal storage of the thymic hormone, thymulin, which results from a secretory function defect. These observations suggest a possible role for the thymic reticulum in thymic function deficiencies.

Ultrastructural studies of thymic reticulum: I. Epithelial [corrected] component.

In studying the epithelial component of the mouse thymic reticulum, we identified by their ultrastructural aspect three types of epithelial cells: type I, present in the cortical and medullary zones; and type II and type III, present only in the medulla. These cells form a network entrapping lymphocytes. In addition, some cells are regrouped and form two types of associations that are found in the medulla: cystic cavities and Hassall's corpuscles [corrected]. Comparisons are made between our observations and those described in older publications. The morphologies and roles of these cells as well as the terminologies used to describe them are discussed in light of the new knowledge acquired concerning the function of the thymus.

Thymus reticulum of autoimmune mice. 3. Ultrastructural study of NOD (non-obese diabetic) mouse thymus.

The non-obese diabetic (NOD) mouse develops spontaneous insulin-dependent diabetes mellitus. Converging lines of evidence indicate that the disease is of autoimmune origin and is primarily mediated by T cells. It thus appeared interesting to study the morphology of the thymic microenvironment in order to determine whether the architecture and/or the cellular components of the organ are altered. In the NOD mouse, significant aspects of involution were observed as early as the first month of life, forming a heterogeneous pattern with non-involuted areas. With time, these involuted aspects increased in surface and severity. In non-involuted zones vacuolization of epithelial cells was noted, as well as infiltration by plasma cells and the presence of numerous macrophages with high phagocytic activity. Involuted areas, forming a cellular layer as if cells had lost their limiting membranes, were crossed by a great number of cystic cavities bordered by epithelial cells and cells containing granulations. Their lumens contained lymphocytes and a few macrophages. These observations, which are reminiscent of similar reports made in other autoimmune mouse strains, may be related to the functional thymic abnormality thought to participate in the pathogenesis of autoimmune disease.

Ultrastructure of a polysome-lamellae complex in a human paraganglioma.

Study of a human abdominal paraganglioma under electron microscopy revealed an unusual cytoplasmic inclusion appearing as a hollow cylinder made up of one or several concentric lamellae surrounded by single or aggregated granules. Cross sections of the lamellar element show a discontinuous juxtaposition of particles. It is moderately dense and is bordered by 140--to 250-A granules of sure ribosomal nature. The inclusion is closely connected to the rough endoplasmic reticulum. The origin and significance of this complex are discussed.

[Histological and ultrastructural study of intestinal ganglioneuromatosis. The multiple endocrine neoplasms type IIb syndrome]. / Etude histologique et ultrastructurale d'une ganglioneuromatose intestinale. Syndrome de néoplasie endocrine multiple du type IIb.

The syndrome known as the Multiple Endocrine Neoplasia type III or type IIb presents a particular histological intestinal lesion: hyperplasia of the myenteric plexus. The electron microscopic study of the plexus of Auerbach in our observation suggests a disequilibrium of the different types of individual axonal sheaths compared to the descriptions of a normal plexus. The possible role of this anomaly in the genesis of intestinal manifestations in this syndrome is here discussed.