Evolution, development and involution of the thymus

We studied the appearance of the thymus primordia of main representatives of the vertebrate evolution, observed these anlages in different places of the branchial region and followed their gradual reduction in phyletic line. On the assumption that the thymus potency has been encoded in evolution, we studied the human thymus ontogeny and described the entodermal thymus primordia not only in the 3rd but also in the 2nd and 4th pouch. We describe a very important contribution of the ectodermal canaliculus, projecting from the 3rd cleft, as well as the participation of the hypobranchial neural placode to the definitive thymus formation. Even though the entodermal thymus primordium in the 2nd pouch has reached an advanced stage, the thymus cannot complete its development because the ento-ectodermal relation is missing. In addition to this dysgenesis, we describe thymic involution in a later fetal period in connection with some malformations and confirm the close relation between the central immune organ and the neuro-endocrine system.     

Antibodies to an antigen of human thymus epithelial tissue common to the epidermis of the skin in malignant myasthenia]

It has been demonstrated by the indirect immunofluorecent technique that many of the sera of patients with myasthenia gravis react with the anticells of the human thymus epithelial tissue. Sorption of the sera with the suspension of the epidermis cells and the homogenates of the tissues of other human organs showed that the epithelial cell antigen with which the sera of patients with myasthenia reacted were epidermal heteroorganic thymus antigens, i.e. common for the thymus epithelium and skin epidermis. The presence of antibodies to the cells of the epithelial tissue of the thymus in the sera of patients suffering from myasthenia gravis permits to suppose the existence of an immunopathological process against the thymus tissue antigens (including the heteroorganic structures of its epithelium) in this disease.     

A thymic factor increasing the blood sugar level.

The thymus extract prepared by using isotonic NaC1 solution causes hyperglycaemy and the thymectomy, too, produces the same effect. Consequently, the active substance of the thymus is produced elsewhere in the organism and being stored within the thymus, gets into the extract by homogenizing its cells. Both the thymectomy and the thymic factor increase the effect of alloxan and this sensitizing effect can be prevented by pretreatment with prednisolone.     

Ontogeny of the thymus gland of a marsupial (Monodelphis domestica).

The gray short-tailed opossum (Monodelphis domestica) has recently been established as a laboratory animal; consequently, its utility as an animal model is enhanced as more of its basic biologic characteristics become defined. To this end, we studied the ontogeny of the thymus gland in M. domestica ranging in age from the day of birth to over three years. In contrast to most Australian marsupials, M. domestica possesses only a thoracic thymus. The thymus is large in neonates and remains large until young adulthood (six months of age). It has a well-defined cortex, medulla and Hassall's corpuscles. At about six months of age, the thymuses of most animals begin to atrophy, the cortex and medulla being replaced by fat. By 28 months of age, about 50% of animals have thymuses that are completely atrophied. Thus, the ontogeny of the thymus of M. domestica appears to be similar to that of eutherian mammals.     

The expression of PAC1 increases in the degenerative thymus and low dose PACAP protects female mice from cyclophosphamide induced thymus atrophy

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with cytoprotective ability mediated by its specific receptor PAC1. In this research, firstly the thymus index and the expression of PAC1 in the normal and degenerative thymus with different gender were assayed; secondly PACAP in different dose was used to treat the female mice with cyclophosphamide (CPS) and the changes in thymus index, the expression of PAC1, histopathology, apoptosis, oxidative status and the caspase 3 activity in thymus were determined and compared. It was found that in the mice of age from 1 to 9 weeks in the stage of sex development, the thymus index was significantly higher in female mice than in male mice. And it was found for the first time that the PAC1 expression level in thymus of female mice was significantly higher than that of male mice and the expression of the PAC1 and PACAP increased significantly in the degenerative thymus induced by CPS. After PACAP was co-injected with CPS to the female mice, it was shown that only low dose (1 nmol/kg) of PACAP promoted the thymus index, inhibited the cell apoptosis, ameliorated the oxidative status and decreased the caspase activity significantly, while high dose (10 nmol/kg) of PACAP had no significant protective effects against CPS-induced thymus atrophy. It was concluded that the expression of PAC1 in the thymus changes in reverse ratio with thymus index and in direct ratio with cell apoptosis and only low dose of PACAP had positive effects against the CPS-induced thymus atrophy.     

Thymic alterations in Plasmodium berghei-infected mice

The primary function of the thymus is to develop immature T-cells into cells that further in the periphery will be able to carry out immune functions. The Literature has shown that thymus can be a target for many pathogens and severe structural alterations take place in this organ during infectious diseases. Here, we investigated if thymus is also a target organ during experimental malaria infection by analyzing the presence of parasites inside the organ and histological alterations in thymuses from Plasmodium berghei NK65-infected BALB/c. After 14 days of infection, parasites were found inside the thymus that presented a profound atrophy with total loss of its architecture. We propose that the presence of parasites in the thymus induces histological modifications that alter the microenvironment, impairing by consequence the successful T cell development. Additional studies are currently being developed in our laboratory to verify if such thymic alterations can influence the systemic immune response to the parasite.     

The annual involution and regeneration of the thymus in hibernating animals and perspectives of its studies in gerontology and stem cell proliferation

Data on a unique phenomenon of annual involution and neogenesis of thymus gland in hibernating animals are reviewed. In accordance with morphological findings, the annual thymus involution in hibernating animals is close to the age-dependent thymus involution occurring in all mammals once in a lifetime. In opposite, thymus involution in hibernating animals is totally different from the accidental involution. During hibernation, the thymus tissue is substituted by the brown fat tissue. In the spring, thymus gland neogenesis stats with intensive growth of epithelial tissue followed by lymphocyte infiltration and exhaustion of brown tissue. Morphological changes in the thymus gland within the annual cycle were compared with seasonal dynamics of structural and functional changes in peripheral lymphoid organs (spleen, lymphoglandular, peritoneal fluid). A general regularity was observed involving a decreased functional activity of immune cells in autumn, its sharp depression during winter hibernation, and obvious increase in summer with the onset of a season of animal activity. It is supposed that a sharp increase in the tumor necrosis factor (TNF) production observed during short-term awakenings in winter may serve an important link in this unique immune adaptation mechanism. The season changes in cellular TNF secretion suggest a mobilization of protective resources in hibernating animals in autumn and winter, i.e. in seasons when the thymus gland activity is depressed. The annual involution of thymus gland cannot be related to droppings in the environmental or body temperatures, as it comes long before their fall. Additionally, it is not related to ageing, as it occurs already in young hibernating animals. The role of hormones, including melatonine and corticosteroids, in mechanisms regulating thymus gland involution in hibernating animals is discussed.     

Acidic pentapeptide phosphorylated in vitro by calf thymus protein kinase NII binds to DNA in the presence of Mg2+ cations

The pentapeptide pyroGlu-Ala-Glu-Ser-Asn has been synthetized and phosphorylated in vitro at level of serine by protein kinase NII isolated from calf thymus chromatin. It is noteworthy that the calf thymus kinase NII shows a remarkable affinity for this peptide. The [32P]peptide is able to bind to several DNAs in the presence of Mg2+ (lambda phage, calf thymus, pBR540 plasmid). This binding appears not specific with regard to the type of DNA and its base sequence. These data support the hypothesis that phosphorylated acidic domains of nuclear nonhistone proteins could bind directly to DNA in the presence of Mg2+ cations.     

Effect of pentoxyl, ibuprofen and acetylsalicylic acid on the thymus, spleen and adrenals in an experiment]

The effect of acetylsalicylic acid, ibuprofen and pentoxyl on the histological and morphometric pattern of the thymus and the weight of the thymus and spleen was studied in rats. There was decreased function of the thymus and its atrophy with acetylsalicylic acid and ibuprofen. Pentoxyl increased the secretory activity of the thymus. The effect of the drugs on the thymus and spleen was unidirectional.     

Effect of triacontanol on numbers and functions of cells involved in inflammatory responses.

A preparation of a triacontanol-containing compound was studied for its effect on cells involved in the inflammatory response. C57BL/6 mice were injected intraperitoneally with various concentrations of this compound and investigated for total body weight, wet weight of thymus tissue, number of thymus cells and splenocytes, interleukin 1 production of spleen monocytes, and response of splenocytes to the T cell mitogen, phytohemagglutinin. Mice treated with the triacontanol preparation exhibited decreased total body weight, 24% reduction in thymus weights, 39% decrease in the number of thymus cells, and 21% depression in total splenocytes. Splenic monocytes of these animals produced a significantly reduced amount of interleukin 1 and splenocytes had a significantly depressed response to phytohemagglutinin. It is concluded that triacontanol has an inhibitory effect on at least some of the cells responsible for inflammation.     

THE ANTAGONISM BETWEEN THYROID AND PARATHYROID GLANDS

From the facts stated in this paper it is evident that the thymus gland of mammals contains a substance which is capable of producing tetany when fed to the larvæ of certain species of salamanders (Ambystoma opacum and Ambystoma maculatum). As long as the larvæ have not developed their own thymus glands, they are able, by means of some mechanism, to counterbalance the tetanic action of the thymus substance introduced in their food. When, however, the secretion from their own thymus glands is added to the thymus material introduced with the food, this mechanism of preventing tetany becomes inadequate and tetany ensues. In the larva of a third species of salamander, Ambystoma tigrinum, this mechanism will prevent tetany even when the larvæ are fed on thymus. In mammals the parathyroids are known to prevent tetany and are supposed either to absorb the tetany-producing substance and thus prevent its action or to change it into another non-toxic substance. It is at least probable that in the amphibians the parathyroids play the same rôle. Larvæ of anuran amphibians, which develop their parathyroids soon after hatching, never show tetanic convulsions if they are fed on thymus, but in certain species of salamanders, whose parathyroids develop only during metamorphosis, the larvæ invariably have tetanic convulsions upon thymus feeding, while the metamorphosed animals never show tetany. But in addition to the parathyroids the salamanders must possess still another mechanism which during the larval period inhibits the production of tetany by the animal''s own thymus glands. In the larvæ of Ambystoma opacum and Ambystoma maculatum this mechanism is sufficient only to prevent tetany from the animal''s own thymus, while in the larvæ of Ambystoma tigrinum it is capable of preventing tetany even when the larvæ are fed with thymus. If the thymus is the organ by whose action tetany is produced, we can understand why tetany in human beings occurs far more frequently in children than in adults, since in the latter the thymus gland is replaced, at least to a great extent, by connective tissue. The relation of thymus to tetany may also possibly explain the occurrence of tetany during pregnancy; while the parathyroids of the mother may be sufficient to prevent tetany from her largely atrophied thymus, they may not be sufficient to prevent tetany from the excess of thymus substance furnished by the fetus to the blood of the mother.     

The thymus in fish: Development and possible function in the immune response

With the exception of Agnatha, fish possess the functional equivalent of the thymus gland found in higher vertebrates. As in other vertebrates, this gland originates from the pharyngeal pouches and ontogenically is the first lymphoid organ to be infiltrated with lymphoid cells. Histology of the structure may differ from one species to another but the cellular component is basically similar. The (paired) gland is surrounded by an epithelial capsule. Within the gland a framework of reticulo-epithelial cells supports the lymphocytes. The age-related involution process, which characterizes the thymus of higher vertebrates, does not necessarily occur in fish. Nevertheless, thymus growth and function may be modulated by those factors that induce its involution such as aging, season, sexual maturity, and stress. The major role played by the thymus in the immune response of higher vertebrates is presumed to occur in fish. Thymus-derived cell dependent immune reactions have been demonstrated in fish. The cells that mediate these functions are designated as T-like cells. So far, cell surface markers equivalent to those of mammalian T lymphocytes have not been characterized. The T lymphocyte specificities are supposed to be acquired within or via the thymic microenvironment. Unfortunately, there is limited data concerned with the cytological and physiological basis of the maturation of thymus-derived cells. Direct involvement of the fish thymus in defense mechanisms has not been investigated extensively. The gland appears to be weakly protected because of its superficial location and is easily exposed to pathogens. Neoplasia is the main pathologic condition reported in the thymus of fish, with little else having been published regarding thymic pathology.     

中国林蛙胸腺类肌细胞的细胞学研究

目的通过对中国林蛙胸腺的组织细胞结构研究,探讨胸腺类肌细胞的结构特点及年周变化规律。方法选用崂山产中国林蛙(Rana chensinensis),雌雄兼有,逐月取材,应用H-E、铅苏木精、Grimelius嗜银和PAS等染色方法进行染色,超微结构用日立透射电子显微镜进行观察。结果类肌细胞是中国林蛙胸腺髓质中恒定出现的一种特征性细胞。细胞质包含许多类似于骨骼肌内的典型结构——肌纤维,根据结构特点可将细胞分为未成熟、成熟以及退化3种类型。肌细胞的出现伴有明显的年周变化,2、3月份开始逐渐增多,到9月份肌细胞的大小与数量达到最大,不同月份所含细胞类型也大有不同。结论类肌细胞是胸腺实质组织中的一种正常细胞,具有不同发育阶段的3种形态结构类型,细胞数量和类型具有年周变化特点,推测与胸腺的正常功能有密切关系。     

Evidence that the Pgp-1 glycoprotein is expressed on thymus-homing progenitor cells of the thymus

The Pgp-1 glycoprotein is found on the bone marrow prothymocyte; however, only a few percent of cells within the normal thymus express significant quantities of Pgp-1 glycoprotein. One hypothesis is that some or all of these Pgp-1+ thymocytes represent thymocyte progenitors or the immediate descendents of the bone marrow-derived prothymocyte. A cell present in the thymus which is able to home back to the thymus and to transiently repopulate it represents one class of thymocyte progenitor. Thymocyte populations enriched in this thymus-homing progenitor are enriched in Pgp-1+ cells. Treatment of these enriched populations with anti-Pgp-1 antibody inhibits activity of the thymus-homing progenitor. These results are consistent with the hypothesis that the thymus-homing progenitor bears Pgp-1 on its surface.     

Epithelial V-like Antigen (EVA), a Novel Member of the Immunoglobulin Superfamily, Expressed in Embryonic Epithelia with a Potential Role as Homotypic Adhesion Molecule in Thymus Histogenesis

Thymus development depends on a complex series of interactions between thymocytes and the stromal component of the organ. To identify regulated genes during this codependent developmental relationship, we have applied an RNA fingerprinting technique to the analysis of thymus expansion and maturation induced in recombinase-deficient mice injected with anti-CD3 antibodies. This approach led us to the identification of a gene encoding a new member of the immunoglobulin superfamily, named epithelial V-like antigen (EVA), which is expressed in thymus epithelium and strongly downregulated by thymocyte developmental progression. This gene is expressed in the thymus and in several epithelial structures early in embryogenesis. EVA is highly homologous to the myelin protein zero and, in thymus-derived epithelial cell lines, is poorly soluble in nonionic detergents, strongly suggesting an association to the cytoskeleton. Its capacity to mediate cell adhesion through a homophilic interaction and its selective regulation by T cell maturation might imply the participation of EVA in the earliest phases of thymus organogenesis.     

Human chorionic gonadotropin binding to rat testis receptors is inhibited by a thymus factor

An interrelationship between immune and reproductive systems has been postulated, and involves, among others, bidirectional effects between gonads and thymus. To this effect a rat thymus fraction of about 28000 mol wt has been reported to inhibit the effect of hCG on in vitro suspension of Leydig cells. We have investigated the antigonadotropin activity of thymus extracts on rat testis receptors. Acetonic powder obtained from thymus of 14 day-old rats was separated by molecular sieve chromatography. The effect of the collected fractions on the 125I-hCG binding to receptor sites in rat testes was evaluated. A fraction corresponding to 27000-28000 mol wt named thymus factor (TF), was found to inhibit the binding activity of 125I-hCG to its testicular receptor. The inhibitory effect of TF on hCG binding is dose related. By Scatchard analysis a competitive interaction at the receptor level between TF and hCG was demonstrated. The Ka values of hCG binding were diminished in the presence of TF while no significative changes were detected in the number of receptor sites. Present results strongly suggest a modulation function of TF at the testis receptor level.     

Expression of atrial natriuretic peptide in thymic macrophages after dexamethasone treatment of rats

Summary The rat thymus represents a site of synthesis of atrial natriuretic peptide (ANP); the immunosuppressor dexamethasone strikingly increases ANP-expression in this immune organ. The presented data suggest that this increase can be attributed to macrophages. By means of immunohistochemistry and Northern blot analysis these immune cells were found to express ANP-immunoreactivity as well as mRNA coding for ANP. In contrast, macrophages of control thymi displayed only weak ANP-immunoreactivity. Thus, ANP appears to be a constituent of rat thymic macrophages, and its synthesis in the thymus is strongly elevated by acute exposure of the animals to glucocorticoids.     

Comparative action of X-rays and fast neutrons on thymus endocrine function

Whole-body exposure of rats to X-rays (4, 6 and 8 Gy) and neutron radiation (1, 1.5 and 2 Gy) causes a dose-dependent inhibition of endocrine function of thymus and death of its lymphoid cells. Shielding of thymus somewhat reduces the degree and duration of inhibition of thymus hormone secretion.     

'DNA snapback' peptides

Thermal denaturation studies show that 10-15% of the calf thymus DNA in the heat denatured (Tyr-Gly-Tyr-Gly-Tyr)-DNA complex renatures spontaneously after colling. The double-strandness of this DNA was verified by its resistance to single-strand Neurospora endonuclease and by its elution profile on hydroxypatite columns. The renatured DNA isolated by the latter technique was found to contain 56% GC compared to the 41% GC content of the whole thymus DNA. Alternating tryptophanyl-glycyl and histidyl-glycyl peptides also catalyze the same renaturation. A linear correlation was found between the thermal stabilization afforded to the DNA by the various peptides and their ability to "catalyze" DNA strand renaturation.