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PubMed1985

[Thymus-hypophysis-thyroid interrelation in rats after administration of a heterologous extract of thymus gland].

The Authors have investigated the effects of a thymus chromatographic fraction on TSH, T3, T4 serum values in thyroidectomized and normal controls rats before and after thymus treatment. The decrease in TSH values of thyroidectomized rats points out a possible inhibitory effect which the thymus extract may have at either the level of the adenohypophysis or hypothalamus. Moreover the TSH values in the euthyroid rats after thymus treatment showed a slight decrease, this changes are much more evident in the thyroidectomized rats after thymus treatment. In fact the plasma TSH of thyroidectomized rats drops from 97.5 +/- 4 microU/ml before thymus treatment, to 76.25 +/- 10 microU/ml after thymus treatment.

Animals↗
PubMed1989

Tolerance induction in the organ-cultured thymus lobes upon intimate contact with allogeneic thymus lobes.

In an organ-cultured murine fetus thymus, precursor cytotoxic T lymphocytes (pCTL) specific for alloantigens developed successfully but those reactive with self antigens were eliminated. In attempting to dissect the mechanism of self tolerance, intrathymic chimera was made by culturing two genetically disparate thymuses in close contact with each other (parabiosis of thymuses). This maneuver resulted in the induction of specific and mutual CTL tolerance. It seems that CTL tolerance was induced by clonal deletion but not by active suppression. Since 2'-deoxyguanosine treatment abolished the tolerogenic capability of the thymus, hemopoietic cells capable of migrating to and fro in the parabiotic thymuses are thought to be responsible for tolerance induction. Induction of CTL tolerance was dependent on the maturation stages of T cells in the thymus: T cells in 5-day-, but not in 7-day-cultured thymuses were susceptible to tolerance induction, indicating that T cells expressing T cell receptors at low density are susceptible to tolerance induction.

Age Factors↗
PubMed1989

Combined grafting of bone marrow and thymus, and sequential multiple thymus graftings in various strains of mice. The effect on immune functions and life span.

The combined grafting of young bone marrow and newborn thymus performed in old mice was effective in restoring the impaired immune functions, but the same treatment performed in middle-aged adult mice had no effect on the life span of C3H/MTV female mice. Sequential multiple newborn thymus graftings starting at young adult age were effective in enhancing immunological functions, delaying the onset of tumor and extending the survival rate to certain degree in the first half of the experimental course in both C3H/MTV as well as C57BL/6 mice, but these effects were not observed in the latter half of the experimental course. It was suggested that multiple newborn thymuses sequentially implanted into the peritoneal cavity underwent atrophy and these atrophic thymuses had a suppressive effect on the host immune system. In autoimmune prone B/WF1 mice, however, the combined grafting of young bone marrow and newborn thymus resulted in suppression of antibody formation to SRBC, and single grafting of either young bone marrow or newborn thymus resulted in a trend of increase in the antibody formation to SRBC. The sequential multiple newborn thymus graftings in B/WF1 mice brought about aggravation of kidney diseases and shortening of the mean life span. On the contrary, administration of thymosin in B/WF1 mice resulted in amelioration of kidney disease and elongation of the mean life span.

Animals↗
PubMed2005

Gene targeting of VEGF-A in thymus epithelium disrupts thymus blood vessel architecture.

The thymus harbors an organ-typical dense network of branching and anastomosing blood vessels. To address the molecular basis for morphogenesis of this thymus-specific vascular pattern, we have inactivated a key vascular growth factor, VEGF-A, in thymus epithelial cells (TECs). Both Vegf-A alleles were deleted in TECs by a complementation strategy termed nude mouse [mutated in the transcription factor Foxn1 (forkhead box N1)] blastocyst complementation. Injection of Foxn1(+/+) ES cells into Foxn1(nu/nu) blastocysts reconstituted a functional thymus. By dissecting thymus stromal cell subsets, we have defined, in addition to medullary TECs (mTECs) and cortical TECs (cTECs), another prominent stromal cell subset designated cortical mesenchymal cells (cMes). In chimeric thymi, mTECs and cTECs but not cMes were exclusively ES cell-derived. According to this distinct origin, the Vegf-A gene was deleted in mTECs and cTECs, whereas cMes still expressed Vegf-A. This genetic mosaic was associated with hypovascularization and disruption of the organ-typical network of vascular arcades. Thus, vascular growth factor production by TECs is required for normal thymus vascular architecture. These experiments provide insights into Foxn1-dependent and Foxn1-independent stromal cell development and demonstrate the value of this chimeric approach to analyzing gene function in thymus epithelium.

Angiography↗
PubMed1970

Studies on thymus function. II. Cooperative effect of newborn and embryonic hemopoietic liver cells with thymus function.

Significant immunological restoration of 45-day old, neonatally thymectomized C3Hf mice was obtained by the cooperation of syngeneic newborn or embryonic hemopoietic liver cells with thymic function. Thymic function or cells alone are almost ineffective or restore approximately 10% of the animals. Newborn liver cells are effective in association with thymus grafts or humoral thymic function (thymoma grafts and thymus or thymomas in diffusion chambers). Embryonic liver cells are ineffective, even in large numbers, when associated with humoral thymic function. On the other hand, embryonic liver cells are effective in the cooperative effect only in association with viable thymus grafts, preferably syngeneic, whether the grafts were placed subcutaneously, intraperitoneally, or under the kidney capsule. Dispersed viable thymic cells are ineffective in association with embryonic liver cells. Cells capable of cooperating with humoral thymic function start to appear to embryonic liver by day 19-21 of gestation and are detectable until day 5-6 postbirth. Embryonic hemopoietic liver cells from 12 to 18 days of gestation contain cells capable of cooperation only with viable free thymus grafts and not with humoral thymic function. A prethymic cell population of partially differentiated cells of hemopoietic origin, insensitive to humoral activity of the thymus but requiring thymic stroma and traffic through the thymus is postulated to explain our results. This population of prethymic cells can become postthymic through this process and eventually develop into competent cells. Postthymic cells are characterized by their sensitivity to humoral activity of the thymus and by their wide distribution in the lymphohemopoietic tissues of newborn and young adult mice.

Animals↗
PubMed1971

Surface immunoglobulins on thymus and thymus-derived lymphoid cells.

Lymphoid cells from thymus, thoracic duct lymph (TDL), and thoracic duct lymph in irradiated animals reconstituted with allogeneic thymus cells (TTDL) were labeled with radioiodinated anti-immunoglobulins using radioautographic techniques. Thymus and TTDL were labeled (14.4 and 37.0%, respectively) with anti-light chain protein after prolonged exposures (30-60 days). No labeling was observed on thymus and TTDL with anti-polyheavy chain globulin. In contrast 18.5-19.0% of TDL labeled on short exposure (6 days) with anti-polyheavy chain and anti-light chain materials. It is proposed that the difference between the labeling observed on short exposures versus long exposures can be related to the difference in surface density of immunoglobulins between nonthymus-derived (B) and thymus-derived (T) cells. The distribution of labeled cells in the thymus was preferentially among the larger cells (greater than 10 micro diameter). The TTDL population was mostly composed of a larger, blast-like population and the distribution of label was independent of size. As the thymus and TTDL preparations contain almost exclusively T cells, this represents a direct demonstration of surface immunoglobulin light chains on T lymphoid cells.

Animals↗
PubMed1988

Thymus in myasthenia gravis. Isolation of T-lymphocyte lines specific for the nicotinic acetylcholine receptor from thymuses of myasthenic patients.

The thymus is believed to play a central role in the pathogenesis of Myasthenia gravis (MG). According to a previous hypothesis, MG is initiated within the thymus by immunogenic presentation of locally produced nicotinic acetylcholine receptor (AChR) to potentially autoimmune T cells. Data of 10 consecutive MG patients demonstrate two critical features of MG thymuses that support the concept of intrathymic activation of autoreactive, AChR-specific lymphocytes. Morphologically, the thymuses showed lympho-follicular hyperplasia in nine cases and benign thymoma in one case. The paramount feature revealed by immunohistological double marker analyses was the intimate association of myoid cells (antigen producing) with interdigitating reticulum cells (potentially antigen presenting cells), both of which were surrounded by T3+ lymphocytes in thymus medulla. All 10 thymuses contained T lymphocytes reactive with AChR. This was in contrast to the peripheral immune compartment (blood) where in only 3 of 10 patients, significant T cell responses to AChR were observed. AChR-specific T cell lines could be established from 8 of 10 thymuses, all members of the helper/inducer subset as indicated by the expression of markers T3 and T4.

Adolescent↗
PubMed2004

Thymus-derived glucocorticoids are insufficient for normal thymus homeostasis in the adult mouse.

BACKGROUND: It is unclear if thymus-derived glucocorticoids reach sufficient local concentrations to support normal thymus homeostasis, or if adrenal-derived glucocorticoids from the circulation are required. Modern approaches to this issue (transgenic mice that under or over express glucocorticoid receptor in the thymus) have yielded irreconcilably contradictory results, suggesting fundamental problems with one or more the transgenic mouse strains used. In the present study, a more direct approach was used, in which mice were adrenalectomized with or without restoration of circulating corticosterone using timed release pellets. Reversal of the increased number of thymocytes caused by adrenalectomy following restoration of physiological corticosterone concentrations would indicate that corticosterone is the major adrenal product involved in thymic homeostasis. RESULTS: A clear relationship was observed between systemic corticosterone concentration, thymus cell number, and percentage of apoptotic thymocytes. Physiological concentrations of corticosterone in adrenalectomized mice restored thymus cell number to normal values and revealed differential sensitivity of thymocyte subpopulations to physiological and stress-inducible corticosterone concentrations. CONCLUSION: This indicates that thymus-derived glucocorticoids are not sufficient to maintain normal levels of death by neglect in the thymus, but that apoptosis and possibly other mechanisms induced by physiological, non stress-induced levels of adrenal-derived corticosterone are responsible for keeping the total number of thymocytes within the normal range.

Adrenalectomy↗
PubMed1988

The entry of the prothymocyte into the thymus after lethal irradiation and bone marrow transplantation. I. Seeding of bone marrow cells into the thymus.

Bone marrow (BM) cells arrive in the thymus of lethally irradiated mice as early as three hours after bone marrow transplantation (BMT). They can be recognized by labeling of the injected cells with Hoechst 33342 (direct homing assay). In order to relate the immigrated BM cells to thymocyte precursor cells, direct homing and thymus repopulation experiments were compared. It was shown that homing of BM cells depends on the time between lethal irradiation and BMT, while it was previously shown that thymus repopulation does not. In addition, thymic immigrants were smaller than precursor cells committed to the T cell limeage (prothymocytes) and their progenitors. A cell population obtained from normal BM cells and enriched in stem cells (purified stem cells) was previously shown to repopulate the thymus similarly as BM cells from mice pretreated in vivo with 5-fluorouracil (FUBM). Both cell suspension showed a delayed thymus repopulation when compared to normal BM. This is indicative for a depletion of prothymocytes in these cell suspensions. In the direct homing assay, however, it was found that relatively many cells from FUBM seeded into the thymus, while purified stem cells did not. These results indicate that most if not all donor cells that are present in the thymus at three hours after BMT are not thymocyte precursor cells.

Animals↗
PubMed1978

Blocking of primary in vitro antibody responses to thymus-independent and thymus-dependent antigens with antiserum specific for IgM or IgD.

The effect of anti-mu and anti-delta on the primary in vitro IgM response of murine splenocytes to thymus-dependent (trinitrophenylated erythrocytes) and thymus-independent (trinitrophenylated brucella) forms of trinitrophenyl was studied. The results indicate that either anti-mu or anti-delta can block the response of adult splenocytes to the thymus-dependent antigen. The thymus-dependent responses of neonatal splenocytes that bear a low concentration of IgD were also abrogated by treatment with anti-delta. In contrast, anti-mu, but not anti-delta, blocked the response of adult splenocytes to the thymus-independent antigen used. These results indicate that both IgM and IgD are receptors required for triggering cells by a thymus-dependent antigen but that only IgM receptors are required for triggering by the thymus-independent antigen used.

Animals↗
PubMed1981

The thymus according to Schambacher: medullary ducts and reticular epithelium of thymus and thymomas.

Thymomas exhibit histologically characteristic features of differentiation with great similarity to structures in fetal, normal and involuted thymus. They include pleomorphic ducts, cysts and glandular structures, which cannot be explained with the conventional views on thymus development as introduced by Hammar, but find a simple histogenetic clarification if Schambacher's concepts are accepted. With suitable fetal material Schambacher's findings can be easily confirmed. They indicate that the thymus is composed of two different types of epithelium, called here the "reticular epithelium" and the "medullary duct epithelium." The origins and development are described. The features of fetal thymus, of normal and involuted thymus, of cystic thymic lesions and of dysplastic thymus are re-examined and compared with structures found in thymomas. The observed findings suggest that thymomas are complex "organoid" epitheliomas with diversified reticular epithelial and medullary duct differentiation. Like other epitheliomas they grow slowly and may show local invasive propensities, but distant metastases remain exceptionally rare.

Adolescent↗
PubMed1988

Alkylation of DNA in F344 rat thymus following administration of 1-n-propyl-1-nitrosourea in vivo and comparison of O6-alkylguanine DNA alkyltransferase activity in thymus from F344 and Long-Evans rats in vitro.

The tissue distribution of radioactivity 1 h after i.p. injection of [n-propyl-2,3-3H]1-n-propyl-1-nitrosourea (PNU) (100 mg/kg) was studied in male F344 rats. This treatment results in a high incidence of thymic lymphomas. The 3H concentration in the thymus, testis and brain was significantly higher than that in blood. 7-n-propylguanine and O6-n-propylguanine were detected in thymus DNA of F344 rats treated with PNU; the ratio of O6-n-propylguanine/7-n-propylguanine was 0.35, lower than following DNA alkylation in vitro. This suggests the presence of O6-alkylguanine DNA alkyltransferase (AGT) in thymus. AGT activity in F344 and Long-Evans rats was compared by using a 3H-propylated DNA as a substrate. AGT activity in the thymus of F344 rats was lower than that in the liver. The AGT activity in the thymus of Long-Evans strain, which had a low incidence of PNU-induced thymic lymphomas, was higher than that of F344 strain. The high level of DNA alkylation by PNU and the low activity of AGT in the thymus may contribute to the high incidence of thymic lymphoma in F344 rat.

Alkylation↗
PubMed1999

[Effect of thymus polypeptide fractions on the development of rat thymus and spleen in organ culture].

Peptides of the thymus--vilon, thymogen and thymalin, alone or in combination with concanavalin A, were used to investigate their effect on organotypic culture of thymus and spleen explants from 1- and 21-day old rats. Vilon, thymogen and thymalin in concentrations of 2 and 10 ng/ml and 5 ng/ml, resp., exerted stimulating effects in thymus and spleen tissue cultures from 21-day old rats as compared to the control explants. Vilon and thymogen showed inhibiting effect in the thymus tissue cultures from 1-day old rats as compared to the control explants. However, the peptides together with concanavalin A in concentration of 10 mkg/ml resulted in decreasing the action of concanavalin A alone. The polypeptide fractions of thymus and their synthetic analogs play different roles in the regulation of thymus and spleen development in rats of different age.

Adjuvants, Immunologic↗
PubMed2005

Evaluation of normal fatty replacement of the thymus with chemical-shift MR imaging for identification of the normal thymus.

PURPOSE: To clarify the influences of age and gender on normal fatty replacement of the thymus in childhood, adolescence, and early adulthood using chemical-shift MRI. MATERIALS AND METHODS: A total of 95 normal subjects (52 males and 43 females, mean age = 15.6 years, range = 7-25 years) who underwent chemical-shift MRI of the thymus were assessed prospectively. Signal intensity loss (SIL) of the thymus was determined by dividing the thymus/muscle ratio on the opposed-phase image by that on the in-phase image. We evaluated SIL for its correlation with age and gender, and assessed SIL of the thymus with uncommon morphological features. RESULTS: A significant correlation was found between SIL and age (r = 0.750, P < 0.001). There was no significant difference in SIL between the genders. No significant SIL was identified in any of the subjects aged 10 years or less. However, significant SIL was found in 70.8% of those aged 11-20 years, 100% of those aged 21 years or more, and 46.2% of subjects with uncommon morphological features of the thymus. CONCLUSION: Chemical-shift MRI can depict physiologic fatty infiltration within the normal thymus in subjects over 11 years of age. It is crucial to correlate these normal age-related findings with clinical cases in order to avoid misinterpretation.

Adolescent↗
PubMed1985

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.

Animals↗
PubMed1984

Repopulation of lymph nodes and spleen in thymus chimeras after lethal irradiation and bone marrow transplantation: dependence on the age of the thymus.

CAP and Lewis rats were thymectomized and received a syngeneic thymus graft followed by lethal irradiation and syngeneic bone marrow transplantation. In three groups (A: recipient 15 months old, thymus graft 3 months old; B: recipient 3 months old, thymus graft 15 months old; C: recipient and thymus graft both 3 months old), we performed an immunohistologic analysis of the splenic white and red pulp and the paracortical zone of the lymph nodes. The repopulation of these regions was demonstrated with monoclonal antibodies that react with Thy-1 positive cells, peripheral T cells, T helper cells, and T non-helper cells. In the splenic red pulp, more Thy-1 positive lymphocytes were found in group B than in group C. The proportion of T lymphocytes and T helper lymphocytes in the region of the periarteriolar lymphocyte sheath of the splenic white pulp was higher when a young thymus was transplanted (groups A and C) than when an old one was (group B). In contrast, in the splenic red pulp, more T lymphocytes were found in group A than in groups B and C. In the paracortical zone of the lymph nodes, this was demonstrable only for group C versus group B. The proportion of T non-helper lymphocytes in the region of the splenic red pulp was higher in group B than in group C. These results indicate that the repopulation of lymph nodes and spleen after transplantation of an old thymus is delayed, quantitatively reduced, and qualitatively different (more T non-helper lymphocytes).

Age Factors↗
PubMed1986

Gangliosides as markers of cortisone-sensitive and cortisone-resistant rabbit thymocytes: characterization of thymus-specific gangliosides and preferential changes of particular gangliosides in the thymus of cortisone-treated rabbits.

Neutral glycosphingolipids and gangliosides in rabbit thymus, spleen, bone marrow, and erythrocyte ghosts were analyzed by conventional chemical and enzymatic procedures and negative ion fast atom bombardment mass spectrometry (FABMS). Thymus gangliosides showed a characteristic composition. Major gangliosides comprising 75% of the total thymus gangliosides were sialosyl lacto-N-neo-tetraosyl- and sialosyl lacto-N-nor-hexaosylceramides containing NeuGc and palmitic acid. These major thymus gangliosides were not detected in spleen, bone marrow, or erythrocytes, whereas GD1a, which was not present in the thymus even in a trace amount, was present in spleen and bone marrow. In addition, the major gangliosides in rabbit thymus were preferentially reduced when an animal was given an intraperitoneal injection of cortisone acetate, as found on analysis 48 h later. The decrease was accompanied by a concomitant increase in NeuAc-containing GM3 with longer chain fatty acids.

Animals↗
PubMed1995

Immunopathology of interleukin (IL) 2-deficient mice: thymus dependence and suppression by thymus-dependent cells with an intact IL-2 gene.

Interleukin (IL) 2-deficient mice develop a fatal immunopathology characterized by lymphoadenopathy, splenomegaly, T cell infiltration of the bone marrow, loss of B cells, anemia, and inflammation of the gut. The thymus dependence of these disease symptoms was tested by introducing the IL-2 mutation into athymic mice. With the exception of an increase in CD8+ intrahepatic alpha/beta T cells, IL-2 deficiency had no detectable effect on leukocyte composition or health of athymic mice, indicating a key role for thymus-derived T cells in the initiation of disease and demonstrating that B cell development and survival are independent of IL-2. In adoptive transfer studies, lymph node and spleen cells from euthymic IL-2-deficient mice induced disease in athymic mice with an intact IL-2 gene, suggesting that thymus-independent IL-2-expressing cells are unable to control the development of immune pathology. Both IL-2+ and IL-2-/- bone marrow cells repopulated the thymus and the peripheral T cell compartment of the recombination activator gene 2-deficient recipients, and chimeras that had received IL-2-deficient bone marrow developed immune pathology. Disease development was, however, fully or at least partially prevented when 30% of the bone marrow inoculum was derived from mice able to express IL-2. These results demonstrate that the IL-2 deficiency syndrome depends on the intrathymic differentiation of T cells carrying the IL-2 mutation, and that the abnormal activation of IL-2-deficient lymphocytes can be controlled by thymus-derived but not thymus-independent lymphocytes.

Animals↗