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Genetic restrictions in the development of antibody responses to L-glutamic acid60-L-alanine30-L-tyrosine10 by nude mice implanted with semiallogeneic thymus glands.

Athymic nude mice implanted with F1 thymus glands were used to investigate genetic restrictions regulating T cell-macrophage (M phi) interactions in the development of antibody responses to GAT. Spleen cells from conventional mice developed comparable primary plaque-forming cell (PFC) responses when stimulated by syngeneic and allogeneic GAT-M phi. However, spleen cells from strain A nude mice implanted with (A X B)F1 thymus glands were tolerant of strain B alloantigens and developed GAT-specific PFC responses to strain A GAT-M phi and allogeneic strain C GAT-M phi, but failed to respond to strain B GAT-M phi. The lack of primary GAT-specific PFC responses by spleen cells from (A X B)thy----A nude mice stimulated by strain B GAT-M phi was not due to detectable suppressor mechanisms. However, an allogeneic effect stimulated by H-2- or non-H-2-disparate GAT-pulsed or unpulsed M phi was able to overcome the inability of spleen cells from (A X B)F1 thy----A nude mice to respond to strain B GAT-M phi. Furthermore, the inability to respond to strain B GAT-M phi was overcome by the addition of supernatant fluids from independent cultures of H-2-disparate cells. These results 1) demonstrate that T cells from A nude mice implanted with (A X B)F1 thymus glands did not recognize nominal antigen in the context of B MHC antigens, and 2) suggested that the T cell repertoire was altered in strain A nude mice implanted with (A X B)F1 thymus glands, such that T cells that could recognize GAT in association with strain B MHC antigens were functionally deleted.

Animals↗

[Model of thymus gland dysfunction].

The thymus dysfunction induced by different doses of lymphocyte-stimulating substance, thymozine, antilymphocyte immunoglobulin and prednisolone effect upon the hormonal-immunologic balance of the hypophyseal-thymus-adrenocortical system, was studied in guinea pigs. It was stated that thymomegalia is accompanied by intensified lymphopoiesis (mainly, owing to T-lymphocytes), somatostimulating hormone and prolactin hypersecretion by adenohypophysis and the adrenocortical glucocorticoid function inhibition. Inverse proportional changes are seen in the thymus hypoplasia. The data obtained may serve as a reliable criterion for physiology and pathology of the thymus and conjugated organs and systems.

11-Hydroxycorticosteroids↗

Age-correlated changes in the lupus erythematosus antigens Ro, La, Sm and RNP of the thymus gland.

The concentrations of the Sm, RNP, La and Ro antigens of thymus glands from rats were determined depending on the developmental stage of the animals. It was found that lupus antigens strongly decrease after birth. Parallel with this change, the activities of the enzymes DNA polymerase alpha and terminal nucleotidyl transferase in the thymus glands drop during maturation and ageing. These biochemical analyses were supported by immunofluorescence studies using human thymus glands. Moreover, it is documented that a redistribution of Sm and Ro occurs during development. Focusing on Sm, fetal thymus glands contain this antigen predominantly in the cytoplasm, while in immature, mature or old animals Sm is found almost exclusively in the nucleus. From these data we conclude that the amounts of the lupus antigens are additional parameters for the age-correlated function of thymocytes.

Aging↗

Tin concentration in the thymus glands of rats and mice and its relation to the involution of the gland.

Tin is an ubiquitous element and thus enters mammals through the food chain. It has never been found to be dysfunctional in either plants or animal tissue and has been regarded as an innocuous background material. Of the many organs and glands that have been analyzed for tin, only the thymus gland exhibits an above average value for tin. A complete study on the tin content in the thymus gland has never been published and this work is an attempt to investigate this subject. Three types of rodents were used in this study; inbred Lewis rats, inbred A/KI mice (a breast cancer prone mouse) and outbred COBS mice (a cancer resistant mouse). The tin analysis of the muscle, spleen, and thymus indicated constant values for the muscle and spleen tissue, but an increase in the thymic tin concentration (ppm) with age. Besides normal aging studies, the animals were administered the disodium salt of dexamethasone-21-phosphate (dexa), which causes rapid loss of lymphocytes from the spleen and thymus but has no effect upon the muscle. Tin concentration in the muscles remained constant, showed a loss from the spleen and an increase in the thymus gland. The increase indicates that the tin was probably located in the medulla of the thymus, which may be the active biochemical site for tin in rodents. When compared to the COBS mice, the A/KI mice showed a non-statistical difference in tin content in the muscle and spleen and statistically significant lower tin content in the thymus gland.

Aging↗

[Diagnostic algorithms of morphological parameters of the thymus gland in the development of various diseases in premature infants].

The authors have investigated the morphological and morphometrical signs of thymus glands in prematurely born children died of different causes and worked out the algorithm of morphological signs coming along with this or that pathology. It was shown, that weight and weighting coefficient of the thymus gland correlate with degree of child prematurity and different causes of death. Drawing up the algorithm of the morphological changes to determine pathology of a thymus gland gave us an opportunity to establish criteria of normal development of a thymus gland and its developmental lagging, hypoplasia, dysplasia, premature atrophy against a background of incomplete pregnancy and different diseases. The data can be used as diagnostic criteria for evaluating morphological structure of the thymus gland of a newborn infant.

Algorithms↗

[What does radiologic diagnosis of the thymus gland accomplish in myasthenia gravis?].

Radiologic imaging in myasthenia gravis is used for the evaluation of pathologic changes of the thymus gland. Computed tomography can demonstrate tumors of the anterior mediastinum in nearly 90% and is therefore superior to conventional radiography. Because of the variety of size and shape of the normal thymus gland, differentiation between normal thymus, follicular hyperplasia and thymoma is rarely possible especially in younger patients. In elderly patients with myasthenia gravis and involution of the thymus gland tumors of the thymus are reliably detected by computed tomography, whereas the ability of computed tomography to predict the histological diagnosis is poor even with intravenous administration of contrast media.

Humans↗

The thymus gland in secondary immunodeficiency.

The microenvironment within the thymus gland and various thymic hormones facilitates the maturation of prothymocytes to functional T lymphocytes. Abnormal thymic morphology is a hallmark feature of several primary and secondary immunodeficiencies. Thymus glands from patients with the acquired immunodeficiency syndrome or graft-vs-host disease and from patients receiving cyclosporine A therapy are depleted of thymocytes, have a striking reduction in thymic epithelial cell mass, and are virtually devoid of Hassall's corpuscles. In malnourished individuals, similar thymic atrophy is present, although the Hassall's corpuscles are present and cystically dilated. Absence of differentiation antigens or anomalous expression of major histocompatibility antigens occurs on thymic epithelial cells in these conditions, and resembles immunologic abnormalities of the thymus in severe combined immunodeficiency. In acquired immunodeficiency syndrome, graft-vs-host disease, and cyclosporine therapy, there is an expansion of cytotoxic/suppressor (CD8) lymphocytes. Experimental evidence suggests that in many situations, such cells may cause damage to the thymic epithelium. The damage to the thymic epithelium may alter the thymic microenvironment and contribute to the immune dysfunction observed in these patients. In addition, a damaged microenvironment may hinder therapeutic efforts to reconstitute immunity.

Acquired Immunodeficiency Syndrome↗

Sulfhydryl blocker-induced colitis in the rat: immunological changes in thymus gland and colonic mucosa.

The study was designed to examine the changes of thymus in sulfhydryl blocker-induced colitis. We used N-ethylmaleimide (NEM) as sulfhydryl blockers. Fasted male Sprague-Dawley rats were given 3% NEM in 1% methyl cellulose into the colon. N-ethylmaleimide treatment caused severe diarrhoea with bleeding for the first 7 days. At autopsy, adhesions, colon dilatation, and single or multiple erosions and ulcers were observed. Time-course studies revealed that the lesions were most extensive and severe 3 or 7 days after the administration of NEM. Histological examination of colon on the 3rd day after NEM treatment demonstrated mucosal erosion, oedema and extensive infiltration of neutrophils. The mucosal lesions extended into the submucosa and muscle on the 7th day after NEM treatment. Immunohistochemical studies showed that T cells and macrophages were markedly increased in the lamina propria of colonic mucosa. After 3 weeks, the infiltration of chronic inflammatory cells was observed and regeneration of the mucosa was noticed. The thymus gland was significantly decreased in weight and size on the 3rd day after NEM treatment, but the weight loss of thymus gland was regained in 3 weeks. Transient atrophy of thymus gland was noticed in this colitis model. The phenotypes of thymocytes were not influenced by NEM treatment. It is concluded that the thymus abnormalities in human ulcerative colitis are not induced in this animal model and that other chronic models are necessary for the elucidation of the immunological abnormalities, including thymus abnormalities.

Animals↗

Effects of gonadal hormones on thymus gland after bilateral ovariectomy and orchidectomy in rats.

This study examined the histological changes that occurred in the thymus gland after gonadectomy and the administration of various sex steroids following gonadectomy. Male and female Wistar albino rats that were 6 weeks of age were used. The rats were subjected to bilaterally gonadectomy and then gonadal steroid hormones (testosterone, estrogen, and progesterone, 2.5 mg/kg) were given. Effects of gonadal steroid hormones on the thymus gland were microscopically examined. Thymic weight increased in all the groups after gonadectomy. Testosterone, estrogen, and estrogen + progesterone treatment decreased thymic weight after gonadectomy. Progesterone treatment also decreased weight, but there was no statistical significance. In the light microscopy, testosterone and estrogen treatment induced a loss of lymphoid elements from the thymic cortex, increased the number of phagocytic macrophages and mast cells, and enlarged blood vessels and connective tissue were observed in the thymic medulla. In the electron microscopic study it was observed that rough endoplasmic reticulum enlarged in the thymic lymphocytes. The same results were also found after estrogen + progesterone treatment. No histologically identifiable changes were observed in the thymus gland after progesterone treatment. This study demonstrated that the thymus gland undergoes involution after testosterone and estrogen treatment, but not progesterone, following gonadectomy.

Animals↗

Reptilian thymus gland: an ultrastructural overview.

Like in higher vertebrates, the thymus gland of reptiles consists of lymphoid cells within epithelial framework and characteristic myoid cells. Mammalian-like Hassall's corpuscles are absent. Secretory cells, secretory and degenerative cysts as well as phagocytic cells, and plasma cells can be observed. Interdigitating cells and some characteristic features of thymic innervation and vascular system are also described in the reptilian thymus gland.

Animals↗

The afferent innervation of the thymus gland in the rat.

The afferent nervous supply to the thymus gland has been investigated by means of the retrograde transport of horseradish peroxidase. It has been shown that the thymus receives an afferent supply from the nodose ganglia of the vagus and from the dorsal root ganglia C1-C7. The afferent innervation of the right and left thymic lobes is bilaterally organized; the fibers of a small celled population of nodose ganglion neurons cross outside the thymus and those of a larger celled population cross within the thymus gland. The functional implications of these findings are discussed in the context of central nervous system-immune system interactions.

Afferent Pathways↗

Pituitary epithelial cell implants reverse the accumulation of CD4-CD8- lymphocytes in thymus glands of aged rats.

Although implantation of GH3 pituitary epithelial cells has been shown to reverse thymic aging in rats, the differentiation pattern of T-lymphocytes within the reconstituted thymus glands has not been investigated. Syngeneic GH3 cells were implanted into 22-month-old female (old) Wistar-Furth rats. Eight weeks later, thymus glands and thymocyte subpopulations were compared to those in aged (24-month-old) and young (3-month-old) female Wistar Furth rats. We confirmed that implantation of GH3 cells increased (P less than 0.05) not only thymus size but also the number of thymocytes isolated from aged rats. Flow cytometric analysis using dual color direct immunofluorescence with fluorescein isothiocyanate-labeled anti-CD4 (W3/25) and phycoerythrin-labeled anti-CD8 (OX 8) monoclonal antibodies revealed that thymus glands from young rats had approximately 20% CD4-CD8- and 30% CD4+CD8+ cells. Thymus glands from old rats contained greater than 50% more CD4-CD8- cells and a reduced percentage of CD4+CD8+ lymphocytes compared to those of young rats (P less than 0.05). Moreover, both of these age-associated changes were reversed (P less than 0.05) by implanting GH3 cells. GH3-treated aged rats also had a significantly (P less than 0.05) greater proportion of CD4+CD8- thymocytes compared to aged control rats. There were no differences among the three groups of rats in the percentage of CD4-CD8+ thymocytes or in the percentage or intensity of cells expressing the T-cell markers CD3, T-cell receptor, or OX19. These results show that in aged rats, intrathymic maturation is inhibited at the key transitional stage where double negative cells differentiate into double positive cells, which may limit the diversity of the T-cell repertoire. The data also extend earlier results by demonstrating that GH3 epithelial cells promote not only growth, but also the differentiation of T-lymphocytes in the aging rat thymus.

Aging↗

The presence of erythroid cells in the thymus gland of man.

Biopsies of the right lobe of normal thymus glands without signs of neoplasia or germinal centre formation from 35 patients ranging in age from 20 to 60 years of age, and from 3 children aged 6, 7 and 12, showed on electron microscopic examination of the material from 14 patients that in 12 cases erythroid cells of all stages of development past the beginning of haemoglobinisation were present in some degree. Earlier erythroid cells could not be identified on morphological grounds with certainty, but cells which could have been lymphoblasts, proerythroblasts and stem cell were all observed. A section of a megakaryocyte was seen in one thymus. The importance of erythropoiesis within the thymus gland is briefly discussed.

Adult↗

The histopathological changes in the thymus gland in the acquired immune deficiency syndrome.

Histologic study of the thymus glands from patients who have died of AIDS reveals changes consistent with an organ-specific immune complex attack by polyclonal immunoglobulins directed against the thymic epithelial cells, Hassall's corpuscles, and certain subsets of thymocytes. This results in marked architectural alteration: there is eventual disappearance of the corpuscles, the epithelial cells become spindled with pyknotic nuclei, there is thymocyte depletion and patchy fibrosis, and there is loss of the normal corticomedullary demarcation. These changes are characteristic and are not found in the normal aging process of the thymus gland. The blood levels of thymic peptides are abnormal. There appears to be specific immunoglobulins directed against thymic epithelial cells, Hassall's corpuscles, and certain subsets of T lymphocytes. The end result appears to be both a histologic and functional thymic disorder. If this is correct, then appropriate therapy for AIDS may be thymic peptide replacement or even thymic transplantation.

Acquired Immunodeficiency Syndrome↗