Takeshi Hoshino

Electron microscopic studies of the epithelial reticular cells of the mouse thymus

SummaryElectron microscopic studies have been made of the epithelial reticular cells of the thymus in mice of both sexes ranging in age from 5 to 8 weeks. The epithelial cells generally have long cytoplasmic processes by which they are interconnected and form a network throughout the organ. The processes adhere tightly to one another by desmosomes. At the surface of the organ the processes constitute a thin sheet, and a basement membrane is discernible close and parallel to the free surface of the epithelial sheet. In the cortex the meshes of the epithelial reticulum are filled with numerous lymphoid cells and relatively few mesenchymal reticular cells. The epithelial cells in the cortex are characterized by their slender cytoplasmic processes and by the presence of large round vesicles which contain coarsely granulated, dense material. By the presence of the vesicles as well as desmosomes at junctions of the cytoplasmic processes the epithelial cells can be distinguished from other cells. For comparison the cytological characteristics of the mesenchymal reticular cells are also described. In the medulla two types — reticular and hypertrophic — of epithelial cells are recognized. The cells of reticular type are irregularly stellated in shape with extended cytoplasmic processes. Their cytoplasm often contains considerable amounts of fine filaments in bundles. Due to the relative abundance of free ribonucleoprotein particles and other cytoplasmic components, the cytoplasm appears relatively electronopaque as compared with that of the cells of the other type. The plasma membrane of the cells of reticular type sometimes invaginates into the cytoplasm to enclose a lumen which contains substance of low density and sometimes fine filaments. A basement membrane-like layer is discernible close to the infolded plasma membrane in the lumen. The cells of hypertrophic type are relatively large and round with a few shorter cytoplasmic processes. They are characterized by the abundance of the smooth endoplasmic reticulum which appears as vesicle or sac of small size. These cells often possess peculiar vesicles the wall of which is provided with microvilli projecting into the lumen. Some of these vesicles carry cilia on their wall in addition to the microvilli. The cells of hypertrophic type often undergo degeneration. The degenerating cells are concentrically surrounded by a few neighboring cells of both hypertrophic and reticular types, and Hassalls corpuscles are formed.

Histological changes of the mouse thymus during involution and regeneration following administration of hydrocortisone

SummaryA histological study has been made of the thymus in mice during acute involution and regeneration following administration of hydrocortisone. The cortex undergoes remarkable changes in the microscopic structure during involution and regeneration. During involution the lymphocytes in the cortex rapidly decrease and are removed. Then a rapid replacement of lymphocytes occurs during regeneration. On the basis of formation and repopulation of lymphocytes the regenerative process of the cortex is divided into seven phases. The reconstitution of the cortex proceeds more rapidly in females than in males. Newly formed lymphocytes take origin from the mesenchymal cells in the cortex. Such mesenchymal cells become distinguishable from epithelial reticular cells during involution. They appear to engulf destroyed lymphocytes and debris during involution and then transform into immature lymphoid cells during early regeneration. The findings may support the recent reutilization concept that destroyed lymphocytes are phagocytized and reutilized by reticular cells in heteroplastic differentiation into immature lymphoid cells. In the cortex PAS-positive sudanophilic cells which are derived from the perivascular and subcapsular connective tissue appear with involutionary changes. They become gradually reduced again with progress of the regeneration of the cortex. During involution the medulla are temporarily filled with lymphocytes migrated from the cortex. The epithelial reticular cells in the medulla are found grouped in cords or clumps in the severely involuted thymus. In the medulla there are two types of PAS-positive epithelial reticular cells; one contains a large, colloid-like, PAS-positive inclusion within the cytoplasm and the other has cytoplasm diffusely filled with PAS-positive substance. During involution and early regeneration, the former type increases while the other shows almost no significant changes. Hassalls corpuscles somewhat increase in frequency during involution and early regeneration.

Fine structure of the epithelial reticular cells of the medulla of the thymus in the golden hamster.

SummaryThe epithelial reticular cells of the thymic medulla of the golden hamster were studied by electron microscopy. On the basis of their structural details two cell types are distinguished, although the two types are similar in basic structure. The cells of one type are more extended in shape and darker in appearance. They are connected with one another by their cytoplasmic processes, forming a reticulum in the medulla. Thus they appear to play a supporting role as do the cortical epithelial reticular cells. The other cell type is larger, more rounded and lighter. The characteristic feature of this cell type is an abundance of vesicular structures, which occur as vesicles or vacuoles of varying sizes. In addition, an enormous, intracytoplasmic ciliated cyst is occasionally encountered in the latter cell type. The cyst may be regarded as representing a specialized form of the vesicular structures. The possible functional significance of the latter cell type is discussed in relation to recent concepts concerning the mechanism of thymic function.

Studies of the influences of pregnancy and lactation on the thymus in the mouse.

SummaryInfluences of pregnancy and lactation on the thymus were quantitatively and microscopically studied in the mouse. Thytnic involution due to pregnancy occurs in later pregnancy and reaches a maximum at parturition. After parturition the involuted thymus regenerates, but lactation has an inhibitory influence on the regeneration. The possible significance of the thymic changes is discussed particularly in relation to the adrenocortical activity. Histologically the cortex exhibits prominent alterations during the involution and regeneration. The pattern of depletion and repopulation of lymphocytes in the cortex is similar to that in other types of acute involution. The medulla also undergoes microscopic changes which are revealed particularly by the histometric examination of its components.

Pathogenesis of thymic lymphoma induced by urethan in mice

In inbred mice of a low leukemic strain, dd, urethan was proved to induce thymic lymphoma when it was repeatedly administered early in life. At the age of 135 to 150 days the incidence of the tumor was 6/23 in males and 12/24 in females. In 8 males (8/17) and 6 females (6/12) of mice macroscopically free of the tumor, the thymus revealed microscopically early neoplastic changes. Thus the cumulative incidence of both neoplastic and early neoplastic cases was 14/23 for males and 18/24 for females. The urethan-induced thymic lymphoma was similar, in both histological characteristics and histogenesis, to that induced by other agents. The early lymphomatous changes appeared as replenishment with immature lymphocytes in the cortex after depletion of cortical small lymphocytes. The changes preceding lymphoma were often found in one lobe only of the thymus. An Mäusen eines japanischen Inzuchtstammes (dd) ließ sich zeigen, daß Urethan ein Thymuslymphom hervorrufen kann, wenn es in den ersten Lebensmonaten wiederholt gegeben wird. Bei 6/23 Männchen und 12/24 Weibchen traten im Alter von 135–150 Tagen makroskopisch erkennbare Tumoren auf. Bei 8 Männchen (8/17) und 6 Weibchen (6/12) von den Tieren, die makroskopisch noch frei von Tumoren waren, zeigte der Thymus mikroskopisch frühneoplastische Veränderungen. Die Häufigkeit der neoplastischen und frühneoplastischen Fälle zusammen war also 14/23 bei den Männchen und 18/24 bei den Weibchen. Das Urethan-Lymphom des Thymus war hinsichtlich Histologie und Histogenese identisch mit den von anderen Agentien erzeugten Lymphomen. Die Frühveränderungen sahen aus wie eine regenerative Proliferation undifferenzierter Lymphocyten in der Rinde. Oft wurden sie nur in einem Thymuslappen beobachtet.

Influences of the gonad on the thymus in the mouse

SummaryIn mice of an inbred Japanese dd-strain, age changes in the thymus weight were studied for both sexes from 5 days until 300 days of age. Further studies were made on effects of gonadectomy on the thymus in both male and female mice which were gonadectomized at 35 days and 100 days of age.1.The thymus grows markedly at the same rate in both sexes in early life until at about 35 days it reaches a maximum in weight. Then it decreases in weight due to age involution. During adolescence and early maturity until about 100 days the decrease in thymus weight is relatively rapid, and it is more prominent in males than in females. During sexual maturity after 120 days until 300 days so far examined, the decrease in the thymus weight is very slow, and the thymus is significantly heavier in females than in males.2.The sex difference in the thymus weight is no longer evident in gonadectomized mice. The thymus of the male responds to castration by a remarkable increase in weight, while the thymus of the female is little influenced by ovariectomy. From these considerations it is surmised that the sex difference in the thymus weight is due to that the thymus in the male is suppressed by the testis, namely, the male gonadal hormone.

Further observations of urethan-induced thymic lymphoma in mice

In mice of a low leukemic strain thymic lymphoma was induced by repeated application of urethan in early life. The thymus was grossly and microscopically examined to elucidate the appearance and development of the neoplastic changes at various ages during the latent period (see Table). The neoplastic transformation of the thymus occurs earlier and proceeds faster in females than in males. The sex difference may be due primarily to an inhibitory action of the testes in the male. In spite of the action of the testes, however, the thymus appeared finally to undergo neoplastic transformation also in males. Bekanntlich kann Urethan ein Thymuslymphom bei Mäusen hervorrufen. In dieser Mitteilung wird das Erscheinen und die Entwicklung der Lymphomentstehung im Thymus während der Latentzeit makroskopisch und mikroskopisch beschrieben (s. Tabelle). Die neoplastische Transformation des Thymus entwickelt sich und erscheint früher bei Weibchen als bei Männchen. Der Geschlechtsunterschied scheint auf einer hemmenden Wirkung vom männlichen Geschlechtshormon zu beruhen. Trotzdem erfährt aber der Thymus auch bei Männchen zuletzt eine neoplastische Transformation.

Histological studies of influences of pregnancy and lactation on the adrenal cortex in mice

SummaryHistological and histometric studies were made of the adrenal cortex of the mouse during pregnancy and lactation. In earlier pregnancy the cortex histologically shows almost no changes, except that the X zone disappears during this period of the first pregnancy. In later pregnancy and at parturition the fasciculata cells are less vacuolated in appearence and relatively large in size, and their nuclei are remarkably enlarged in volume. After parturition the histophysiological findings of the fasciculata cells are different between lactating and non-lactating mice. In lactating mice the fasciculata cells show a marked increase in vacuolation and a striking enlargement of the size. Their nuclei are also hypertrophie. In non-lactating mice, the fasciculata cells are almost the same both in vacuolation and in size as those of normal females, although their nuclei remain somewhat large in volume. These results are discussed particularly in relation to the thymic changes dealt with in a previous paper (Ito and Hoshino 1962): the histophysiological findings of the fasciculata would give an explanation for the thymic changes during pregnancy and lactation.