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PubMed1996

Histogenesis of the epithelial component of rat thymus: an ultrastructural and immunohistological analysis.

BACKGROUND: Despite the assumed importance of thymic cell microenvironments for governing T-cell maturation, little is known about the ontogeny of their cell components. A few studies have analyzed previously the ontogenetical development of rat thymic epithelium (Bogojevic et al. 1990. Period. Biol., 92:126; Kampinga and Aspinall 1990 Harwood Acad. Pub., London, pp. 149-186; Micic et al., 1991 Dev. Comp. Immunol., 15:443-450) and recently we have reported the development of both interdigitating/dendritic cells and macrophages (Vicente et al., 1994 Immunology, 82:75-81, 1995 Immunology, 85:99-105). METHODS: In the present work we analyze in situ ultrastructural, immunohistochemical, and histoenzymatically the appearance and development of the thymic epithelial cell component in both embryonic and neonatal Wistar rats with special emphasis on the origin of the different epithelial cell types, the occurrence or absence of a common precursor for these, and the expression of MHC molecules. RESULTS: The thymic primordium of 13-day-old embryos is formed by a homogeneous population of primitive epithelial cells differentiating gradually into various epithelial cell subtypes of both the cortex and the medulla. In the cortex, subcapsular and stroma-supporting epithelial cells appear at days 14-15 as two structurally different cell entities. At the same time, stroma-supporting, keratinized, and vacuolated epithelial cells occur in the thymic medulla. These last two cell types differentiate subsequently into Hassall's bodies and hypertrophied cells. Lympho-epithelial cell complexes are identified in the deep cortex around birth, when the cortical parenchyma houses a transitional erythropoiesis. mAbs (His-39, RMC-20) which recognize medullary epithelial cells in the adult thymus stain positively cells of the thymic primordium as early as day 16 of embryonic life. Cortical epithelial cell markers (His-37, RMC-17) appear, however, slightly later and the subcapsulary region is not established until postnatal life. MHC class I and class II molecules can be identified on epithelial cells in the thymus of 15-day-old embryonic rats although they reach the highest expression around birth. CONCLUSIONS: Our results confirm the heterogeneity of the thymic epithelial component, the persistence of primitive, non-differentiated epithelial cells morphologically similar to those occurring in the early thymic primordium in adult thymus, and the mutual relevance of epithelial cells and thymocytes for an adequate development of rat thymus gland.

Animals↗
PubMedDate not supplied

Ovarian development in athymic nude mice V. The effects of PMSG upon the numbers and growth of follicles in the early juvenile ovary.

The composition and growth patterns of the ovarian follicle population have been determined in early juvenile athymic nude mice and their phenotypically normal littermates. Nude ovaries contained significantly more primordial follicles and fewer trilaminar follicles at 10 days of age. The rate of growth of the oocyte nucleolus was significantly less than in control ovaries. Treatment with PMSG from days 7 to 9 restored the rate of oocyte nucleolar growth in nudes to control levels. PMSG also increased the number of follicles commencing growth in both nudes and controls and the differences in the numbers of primordial and trilaminar follicles were no longer detectable. The data demonstrate that abnormalities in the ovarian follicle population of the nude are detectable as early as the 10th day of life and can be reversed by treatment with exogenous gonadotrophin. These results are discussed in relation to the role of the thymus gland in ovarian development and the competence of the early juvenile ovary to respond to gonadotrophin.

Animals↗
PubMed2001

[The ubiquitin system--structure and function].

Current opinions connected with the role and significance of ubiquitous proteins--ubiquitins (Ub) were discussed. Genetic determination of ubiquitins and their expression in nature were considered. Thymic ubiquitin complex, as an extract from calf thymus gland (TFX) was also presented. Very important biological activities in some experimental models and usefulness of TFX in medical practice were presented.

Animals↗
PubMed1984

Somatostatin has an antiproliferative effect on concanavalin A-activated rat thymocytes.

Somatostatin, a cyclic tetradecapeptide which is widely distributed in different tissues of the body, exerts an inhibitory effect on numerous cellular processes. It has been observed recently that somatostatin and its analogs were antimitogenic in several established cultured cell lines and in rat tumors. To determine whether this ubiquitous peptide had an antiproliferative effect on a primary culture of rat thymocytes, we observed its effect on the separation of the centrosome (a cell maker of the G1 to S traverse) and DNA synthesis of rat thymocytes activated by concanavalin A. Somatostatin inhibited both indices of proliferation in rat thymocytes at a concentration of 10(-8)M. This observation suggests that somatostatin, which has been localized in the thymus, may play a regulatory role in the growth and development of the cells found in the thymus gland, and may affect thymocyte function in disease states characterized by elevated circulating concentrations of somatostatin.

Animals↗
PubMed1991

Rise in thymocyte number and thymulin serum level induced by noise.

A high level of noise is known to induce important changes in the immune system. In this work, the effect of sound stress on the circulating level of thymulin and on the cellularity of the thymus gland was studied. The experiments were done in RK mice exposed to a noise level of 100 dB for a period of 1 h. Following the noise exposure, the animals were bled at different times for thymulin titration, or killed in order to evaluate the number of cells and the weight of each thymus. The results indicate that young mice exposed to the stressor stimulus show an increase in serum thymulin titre, and at the same time they show an increment in thymus weight and in thymocyte number compared to control. These results support a new argument in favour of the theory of a central nervous system control on the thymus function.

Age Factors↗
PubMed1986

Autoimmune effector cells. VII. Cells isolated from thymus and spinal cord of rats with experimental allergic encephalomyelitis transfer disease.

Effector cells mediating experimental allergic encephalomyelitis (EAE) were recovered from the thymus glands and spinal cords of Lewis rats immunized with myelin basic protein (BP) and complete Freund's adjuvant (CFA), as demonstrated by adoptive transfer to syngeneic recipients following in vitro activation with BP. The thymic effector cells (TCs) were lymphoblasts. Sequential transfer studies suggested that the effector TCs probably recirculated back to the thymus from the periphery. The transfer of EAE with cells derived from the spinal cords of paralyzed donors indicates that disease-inducing effector cells are present in the target organ.

Animals↗
PubMed1980

Induction of diverse arterial and myocardial lesions by adrenal regeneration hypertension in Sprague-Dawley versus spontaneously hypertensive rats.

Nonarteriosclerotic, virgin, Sprague-Dawley (SD), and spontaneously hypertensive (SHR) rats and arterio sclerotic breeder SD and SHR rats were subjected to adrenal regeneration-induced hypertension (ARH) with and without extra salt. ARH caused a marked increase in the blood pressure of SD rats and a mild increase in SHR rats; extra salt caused exacerbation of hypertension in SD rats only. Heart and kidney weights were greatly increased commensurate with blood pressure. Increased adrenal weight concomitant with thymus gland involution was considerable in SD and less marked in SHR rats. Testes and ovaries were involuted. Creatine phosphokinase and lactic dehydrogenase levels were abnormally high; blood triglycerides, FFA, glucose, and corticosterone decreased, and total cholesterol, glucose, and corticosterone increased in SD but decreased in SHR rats. Blood urea nitrogen levels were much more abnormally elevated in SD than in SHR rats. ARH did not induce arterial disease in the virgin SD or SHR rats, but it did produce a spectrum of arterial disease in SH breeders, e.g. aortic sclerosis, polyarteritis nodosa-like lesions, intimal cartilaginous metaplasia, and hyalin fibrosis. Altered adrenocortical steroidogenesis may have conditioned the arterial wall of SHR rats to develop diverse morphological changes, and extra salt is much more detrimental to normotensive rats (SD) than to genetically hypertensive rats.

Adrenal Glands↗
PubMed1987

Androgen receptors in human thymocytes.

On the basis of a variety of evidence androgenic hormones are thought to exert modulatory effects on immune function. Because specific actions of these hormones are exerted through receptor-mediated mechanisms, we have examined the human thymus gland for the presence of specific high-affinity androgen receptors. Cytosolic extracts of whole human thymus were found to contain 6.5 (+/- 2.6) fmol of specific [3H]methyltrienolone binding per mg protein. The receptor sedimented at 8s on sucrose density gradient centrifugation analysis. Thymic fibroblast lines derived from these glands did not express sufficient receptor content to account for the findings in whole thymus cytosolic extracts. Purified thymocyte preparations (greater than 99.3% pure as assessed by flow cytometry with monoclonal anti-thymocyte marker OKT11) contained 3.34 (+/- 1.2) fmol receptor per mg cytosolic protein. Mature peripheral blood lymphocytes, human T cells obtained from thoracic duct drainage, and the human T cell line Jurkat were not found to contain these receptors. These studies demonstrate for the first time that a high affinity androgen receptor is present in maturing human thymocytes. A functional role for these receptors is suggested by dihydrotestosterone-mediated decreases in interleukin 2-like activity produced by cultured human thymocytes.

Binding, Competitive↗
PubMed1987

Epithelial-cell architecture during involution of the human thymus.

One hundred thymus glands were assessed histologically as to their degree of involution. Epithelial cells were demonstrated by an immunoperoxidase method using a monoclonal antibody against cytokeratin. The distribution of these cells was studied in the medulla, the cortico-medullary junction, the cortical parenchyma and the subcapsular cortex. As involution proceeds, the loss of cells from the thymus is almost totally confined to the lymphoid-cell elements. The architecture of the epithelial-cell network remains largely intact although there is extensive collapse of the structure due to the loss of the intervening lymphocytes. Even when involution is apparently complete; sheets of epithelial cells can be demonstrated in the thymic remnant.

Adolescent↗
PubMed1984

Macrophage subpopulations regulate intrathymic T-cell development. II: Ia-negative macrophages decrease thymocyte viability and proliferation by formation of thymocyte-macrophage-rosettes.

The influence of H2-Ia-negative macrophages (Ia-M phi) on thymocyte viability and proliferation was investigated. Peritoneal as well as Ia-M phi of thymic origin were used in this study and yielded similar results. Cocultivation of thymocyte with 4.5% Ia- M phi diminished thymocyte viability by about 70% and mitogen-induced proliferation by about 90% in comparison to control cultures without addition of M phi. These suppressive effects were related to rosette formation between thymocytes and Ia- M phi: more than 80% of Ia- M phi formed rosettes with immature thymocytes. Mature thymocytes (i.e. PNA-negative, steroid-resistant cells) rosetted in only 5% and were consequently not affected by M phi-mediated suppression. Since Cytochalasin B, known to inhibit rosette formation, abolished the suppressive effects of M phi, and supernatants of M phi cultures exhibited no inhibition of thymocytes, close cell contact (rosette) is apparently necessary for the inhibitory phenomenon. Suppression, however, seems to depend further on the functional state of the M phi: ingestion of carbon particles significantly diminished the inhibitory effect on thymocytes despite further presence of rosettes. The results suggest that Ia- M phi have a regulatory function within thymus physiology. While Ia+ M phi promote thymocyte proliferation as described elsewhere, the Ia- M phi may control the number and kind of thymocytes released by the thymus gland.

Animals↗
PubMedDate not supplied

Chronic diabetes followed by chronic cerebral ischemia induced by bilateral carotid artery ligation in arteriosclerotic versus nonarteriosclerotic rats.

Male and female, arteriosclerotic (breeder) and nonarteriosclerotic (virgin), Sprague-Dawley rats were made severely diabetic with alloxan. Two weeks later experimental animals had both carotid arteries ligated to induce a state of acute cerebral ischemia. After six weeks of cerebral ischemia either with or without severe diabetes the animals were killed. Animals which survived either the acute induction of diabetes or cerebral ischemia did not manifest any new episodes of cerebral ischemia. Subjects with combined diabetes and cerebral ischemia manifested the greatest loss in body weight, adrenal hypertrophy and thymus gland involution, increased levels of serum CPK and SGOT, but decreased SGPT and LDH, hyperglycemia and hypertriglyceridemia, and the most extensive cerebral edema. It is suggested that diabetic rats may have a greater predilection toward cerebrovascular accidents because the diabetic state contributes not only to an exacerbation of atherosclerosis, but also complicates any condition of cerebrovascular ischemia by creating extracerebral edema.

Adrenal Glands↗
PubMed1994

The migration of bone marrow cells to thymic culture supernatants is inhibited by stress.

The effect of immobilization stress on precursor cell migration from bone marrow to the thymus was studied in C57BL/6 mice. The in vitro migration assays, using Nucleopore chambers, showed that precursor cell migration to thymus supernatants was strongly inhibited in stressed animals. This inhibition of migration seemed to be cell-associated what can explain the thymic involution observed in mice under stress conditions. The migration of precursor cells from bone marrow may be one of the mechanisms by which the thymus gland is involuted by stress.

Animals↗
PubMed1976

Cardiac and other abnormalities in the sudden infant death syndrome.

Many victims of the sudden infant death syndrome (SIDS) have abnormally heavy cardiac right ventricles. The degree of this abnormality is directly proportional to: a) the mass of muscle about small pulmonary arteries, b) the amount of brown fat retention about adrenal glands, and c) the presence of hepatic erythropoiesis. The pulmonary arterial abnormality is probably the result of chronic alveolar hypoventilation, while brown fat retention and hepatic erythropoiesis are likely consequences of chronic hypoxemia. These abnormalities are found in both SIDS victims who die with and those who die without mild respiratory tract infections. However, there are some differences between the two SIDS groups. Infected victims die at an older age and have smaller thymus glands and larger spleens; there is a greater proportion of males in the infected victims than in the noninfected victims.

Adipose Tissue, Brown↗
PubMed1991

Effect of dietary fats on the fatty acid compositions of serum and immune tissues in chickens.

The purpose of the present study was to measure the effect of dietary fat source on the fatty acid composition of immune cells in chickens. One-day-old female chicks were fed corn and soybean meal-based diets containing 7% of either lard, corn oil, canola oil, linseed oil (LO), or menhaden fish oil (FO). After being fed experimental diets for 3 to 4 wk, samples of serum, thymus glands, bursa of Fabricius glands, and splenocytes were collected. All samples were frozen and stored at -80 C until lipid analysis. Results indicate that the fatty acid composition of the sera and immune tissues of chickens reflected the fat in the diet. The relative content of long-chain polyunsaturated fatty acids varied considerably among immune tissues, with, from greatest to least, spleen, bursa, and thymus. The young chick demonstrated a substantial capacity to elongate and desaturate linoleic (C18:2n-6) and alpha-linolenic acids (C18:3n-3). Feeding chicks fats rich in n-3 fatty acids (e.g., LO or FO) decreased significantly (P less than .05) the level of arachidonic acid (C20:4n-6) present in the serum and immune tissues by 50 to 75%. The levels of eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C20:6n-3) were substantially increased (P less than .05) by FO and LO feeding. However, LO, which is rich in C18:3n-3, was generally only one-half to one-quarter as effective as FO in elevating EPA and DHA levels in immune tissues. The implications for these changes in serum and immune tissue fatty acid profiles are discussed briefly.

Animals↗
PubMed1993

[Ultrastructural study of the thymus in patients with myasthenia gravis].

The ultrastructure of the thymus gland from ten patients with myasthenia gravis was studied and compared with that from three normal subjects. Thymic substance in myasthenia gravis showed inflammatory reaction characterized by presence of neutrophils and macrophages, plasma cell infiltration, epithelial reticular cell hyperplasia, and new germinal center formation. In contrast lymphoblasts and plasma cells were not present and there was no new germinal center formation in the thymus of normal subjects. It is suggested that humoral immunity plays an important role in the pathogenesis of myasthenia gravis. The function of the myoid cells and the significance of the secretory granules in epithelial cells could only be defined by ultrastructural study.

Adolescent↗
PubMed2003

Exercise training increases the näive to memory T cell ratio in old mice.

Aging is associated with changes in T cells including involution of the thymus gland and an imbalance in the proportion of näive (CD44lo) and memory (CD44hi) T cells in the periphery. Reversal of these changes may improve immunity in the aged. We sought to determine whether 4 months of moderately intense treadmill running (EXC; 5 days/week, 45 min/day, 13-22 m/min) in 2 month (Y) and 18 month (O) old male Balb/c mice would alter T lymphocyte profiles in the thymus and spleen when compared to sedentary controls (CON). Splenocytes and thymocytes were harvested 24-48 h after the last exercise session and analyzed using immunofluorescence and flow cytometry. While there were significant age-related changes (lower cell number, altered subsets) in the thymuses of O when compared to Y mice, exercise training failed to affect any of these measures in mice of either age. Aged mice exhibited a significantly (p < .05) higher percentage of splenic memory cells and a lower percentage of näive cells in both the CD4 and CD8 T cell subsets. Interestingly, exercise training significantly (p < .05) increased the percentage of näive and decreased the percentage of memory cells in both the CD4+ (69.6+/-1.7% näive and 30.4+/-1.7% memory for OCON vs. 75.0+/-1.5% näive and 25.0+/-1.5% memory in OEXC) and CD8+ (60.0+/-2.6% näive and 40.0+/-2.6% memory in OCON vs. 76.7+/-2.7% näive and 23.3+/-2.7% memory in OEXC) T cells subsets in O, but not Y, mice. This effect was due to a decrease in the absolute number of memory cells and not an increase in the absolute number of näive cells. We conclude that 4 months of EXC has little restorative effect on the thymus in aged mice, but can restore the percentages of näive and memory cells in the spleen towards that of young mice, perhaps due to removal of memory cells.

Aging↗
PubMed1991

Bone metabolism and repair are normal in athymic rats.

Several reports indicate that the thymus gland is important in the regulation of bone metabolism. Anatomic or physiologic abnormalities in the bones of athymic animals could therefore be expected. The mechanical properties, circulation, and mineralization rate of intact femora, tibiae, ossa ilia, and of an osteotomized tibia of athymic Lewis rats were compared with those of normal Lewis rats. The results were not significantly different in the two groups. The absence of the thymus thus does not seem to have any major influence on bone structure, function, or regenerative properties.

Animals↗