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PubMedDate not supplied

Ontogeny and thymus-dependence of T cell surface antigens in Xenopus: flow cytometric studies on monoclonal antibody-stained thymus and spleen.

Recently generated anti-Xenopus T cell monoclonal antibodies (mAbs) to the 120 kDa XTLA-1 determinant and against the putative CD5 and CD8 homologues, together with anti-IgM and anti-MHC class II mAbs, are used in dual colour flow cytometric experiments to characterize cell surface antigenic expression on lymphocytes in thymus and spleen of Xenopus laevis during larval and early adult life and also in metamorphosis-inhibited animals. Histological confirmation of T cell emergence early in larval ontogeny is supplied by cryostat sections stained for CD8. Five-day thymectomy, i.e. prior to T-lineage cell differentiation in the thymus, abolishes T cell marker expression in the spleen for up to 1 year. Moreover, late larval (20 days) or early adult (3 months) thymectomy (i.e. removal after peripheralization of T cells has occurred) also leads to severe depletion of mAb-defined T cells in the spleen.

Animals↗
PubMed1992

Radioresistant cells of thymus--producers and targets of thymocyte growth factor and their possible role in postradiation restoration of thymus.

In the present study the association between the damaging and the stimulating action of radiation on the cells of thymus (in particular intrathymic T-lymphocyte precursors, TLP) is analyzed. The radioresistance and possibility to secrete humoral products, in particular, the thymocytes growth factor, THGF, is assessed. The possible role of THGF in the postradiation restoration of thymus is also discussed.

Animals↗
PubMed2003

A developmental look at thymus organogenesis: where do the non-hematopoietic cells in the thymus come from?

The origins of the non-hematopoietic cell types that comprise the thymic stroma remain a topic of considerable controversy. Three recent studies, using lineage analysis and other methods to determine the developmental potential of specific cell types within the thymus, have provided strong evidence of a single endodermal origin for all thymic epithelial cells. Together with other investigations that merge immunological and developmental biology approaches, these studies have suggested a new model of thymus organogenesis, and have begun to uncover the molecular pathways that control this process.

Animals↗
PubMed1975

Transcription of fractionated calf thymus chromatin by RNA polymerase of calf thymus and Escherichia coli.

Calf thymus chromatin has been sheared and fractionated on sucrose gradients. Approximately 5-10% of the chromatin is resolved from the bulk of the imput chromatin as a slowly sedimenting fraction. The protein/DNA ratio of the slowly sedimenting fraction is not greatly different from the protein/DNA ratio of the more rapidly sedimenting chromatin fraction. Analysis of DNA of the chromatin fractions by CsC1 equilibrium density gradient centrifugation indicates that DNA of the slowly sedimenting fraction is depleted in the satellite DNA banding at 1.716 g/cm3. The template properties of the chromatin fractions have been examined with Escherichia coli RNA polymerase and form II and form III RNA polymerases of calf thymus. At rate-limiting concentrations, the slowly sedimenting fraction is twofold more active than the rapidly sedimenting fraction as a template for E. coli RNA polymerase. Homologous form II and form III RNA polymerases are respectively 30-fold and 16-fold more active with the slowly sedimenting fraction than the rapidly sedimenting fraction. The activity of form II RNA polymerase in transcribing the slowly sedimenting fraction exceeds its activity in transcribing an equal concentration of native DNA. Kinetic studies, in which RNA polymerase activity is assayed at various concentrations of chromatin, indicate that the greater activity of E. coli RNA polymerase with the slowly sedimenting fraction is due to an increased rate of transcription at saturating concentrations of template (Vmax), and is not due to a lower concentration required for half-maximal rate of transcription (Km). In contrast, the increased rates of transcription of the slowly sedimenting chromatin faction by the homologous polymerases are due to a decrease in concentration required for half-maximal rate of transcription rather than an increased rate of transscription at saturation concentrations of template. The relative degrease of satellite DNA in the slowly sedimenting fraction of chromatin and the enhanced template activity of the slowly sedimenting fraction suggest that this fraction is equivalent to nuclear euchromatin while the more rapidly sedimenting chromatin is equivalent to nuclear heterochromatin.

Animals↗
PubMed2006

Effect of thyme essential oils (Thymus hyemalis and Thymus zygis) and monensin on in vitro ruminal degradation and volatile fatty acid production.

The effect of the essential oils of thyme on the in vitro ruminal degradability of a barley seed/alfalfa hay substrate was studied. Two essential oils were used, one from Thymus hyemalis (TH), rich in carvacrol, and the other from Thymus zygis (TZ), rich in thymol. Four experimental treatments of in vitro degradability, using the Daisy II(200/220) incubator, were conducted including a negative control (CO), a positive control at 7.5 microg/mL of monensin (MO), and two treatments with essential oils (TH or TZ) at 1.35 microL/mL. The material was incubated at 39.5 degrees C for various lengths of time. At each time, the disappearance of dry matter, crude protein, and neutral detergent fiber was measured. Volatile fatty acids (VFAs) were determined after 48 h of incubation. CO and MO provided (p < 0.01) higher values of potential degradability (a + b) of DM than the TH and TZ treatments (72.6 and 70.8 vs 53.2 and 48.2%, respectively). Also, crude protein degradability was lowest in the essential oil treatments. The CO treatment showed the highest potential degradability of NDF. The values of VFA production obtained (p < 0.001) with CO and MO treatments were higher than those obtained with TH and TZ treatments (21.0 and 19.1 vs 11.2 and 10.1 mM). The essential oils decreased the molar proportion of propionate, increasing the acetate/propionate ratio. In conclusion, the effects of essential oils at assayed doses would not be nutritionally beneficial to the ruminal energetic metabolism.

Animals↗
PubMed2002

The discovery of thymus function and of thymus-derived lymphocytes.

For centuries the thymus remained an enigmatic organ with unknown functions. The first demonstration of its crucial role in establishing the development of a normal immune system was provided in 1961, when it was shown that mice thymectomized immediately after birth had poorly developed lymphoid tissues, impaired immune responses and inordinate susceptibility to intercurrent infections. Although thymus lymphocytes were believed to be immunoincompetent, it was shown in 1967 that they could respond to antigen by proliferating and giving rise to a progeny of cells that could not produce antibody, but enabled other lymphocytes, derived from bone marrow, to differentiate to antibody-forming cells. This was the first unequivocal demonstration, in mammalian species, of the existence of two major interacting subsets of lymphocytes, T and B cells. It required a re-evaluation of many immunological phenomena, such as tolerance, memory and autoimmunity, and it was followed by an avalanche of work elucidating many of the mysteries of the immune system.

Allergy and Immunology↗
PubMed1966

Role of the thymus in tolerance. 3. Tolerance to bovine gamma globulin after direct injection of antigen into the shielded thymus of irradiated rats.

Rats subjected to high doses of whole-body irradiation, with simultaneous shielding of the thymus or spleen, recovered at 3 wk the ability to develop delayed sensitization and to form hemagglutinating and precipitating antibody following foot-pad injection of BgammaG in complete adjuvant. Injection of BgammaG into the shielded thymus immediately after irradiation, in amounts between 20 gammag and 40 mg, inhibited these response to later challenge partially or completely. A comparable effect on immune responses to BgammaG was not seen after injection of heterologous antigen (Ea) intrathymically, BgammaG intraperitoneally, or BgammaG into the shielded spleen. However high doses (20 or 40 mg) of antigen given by the latter routes resulted in some diminution of later response. Arthus reactivity recovered partially in the spleen-shielded group and was readily suppressed by intrasplenic administration of antigen.

Animals↗
PubMed1992

Thymus-independent development and negative selection of T cells expressing T cell receptor alpha/beta in the intestinal epithelium: evidence for distinct circulation patterns of gut- and thymus-derived T lymphocytes.

We demonstrate that mouse intestinal intraepithelial lymphocytes (IEL) can be divided into subsets based on the differential expression of functional T cell receptor alpha/beta (TCR-alpha/beta) signaling complexes. Two subsets, CD4+ 8 alpha + beta - and CD8 alpha + beta -, are refractory to stimulation with anti-TCR-alpha/beta and contain high frequencies of potentially self-reactive cells. In contrast, the CD4+ and CD8 alpha + beta + IEL subsets are responsive to anti-TCR-alpha/beta and depleted of potentially self-reactive cells. The analysis of fetal liver radiation chimeras using adult thymectomized recipients demonstrates that the four TCR-alpha/beta + IEL subsets are generated in normal numbers in the absence of the thymus. Moreover, expression of the major histocompatibility complex class II-encoded I-E molecule and Mls1a in the gut of the athymic host results in the negative selection of potentially self-reactive T cells expressing V beta 11 and V beta 6, respectively, from those IEL subsets that express functional TCR-alpha/beta signaling complexes. Neither the spleen nor the Peyer's patches of athymic recipients contain T cells of donor origin. In contrast, normal numbers of phenotypically and functionally mature CD4+ and CD8 alpha + beta + T cells of donor origin are found in the lamina propria of chimeric animals. The phenotypic analysis of lymphocytes obtained from Ly5 congenic parabionts reveals that peripheral T cells migrate rapidly to the Peyer's patches and lamina propria, but not to the intestinal epithelium. Taken together, these results demonstrate that the intestinal epithelium is a thymus-independent site of T lymphopoiesis, where selection of the T cell repertoire involves the deletion of potentially self-reactive cells in situ. Moreover, the appearance of donor-derived, phenotypically mature T cells, exclusively in the lamina propria of athymic radiation chimeras, suggests that mature IEL expressing functional TCR-alpha/beta migrate to this site.

Alleles↗
PubMed1997

Role of the thymus in transplantation tolerance in miniature swine. I. Requirement of the thymus for rapid and stable induction of tolerance to class I-mismatched renal allografts.

The almost uniform failure in transplant patients of tolerance-inducing regimens that have been found to be effective in rodents, has made it necessary to examine large animal models before testing of new approaches clinically. Miniature swine have been shown to share many relevant immunologic parameters with humans, and because of their reproducible genetics, have proved extremely useful in providing such a large animal model. We have previously shown that indefinite systemic tolerance to renal allografts in miniature swine is induced in 100% of cases across a two-haplotype class I plus minor histocompatibility antigen disparity by a 12-d course of Cyclosporine A (CyA), in contrast to irreversible rejection observed uniformly without CyA treatment. In the present study, we have examined the role of the thymus during the induction of tolerance by performing a complete thymectomy 21 d before renal transplantation. This analysis demonstrated a striking difference between thymectomized and nonthymectomized animals. Thymectomized swine developed acute cellular rejection characterized by a T cell (CD25(+)) infiltrate, tubulitis, endothelialitis and glomerulitis, and anti-donor CTL reactivity in vitro. Nonthymectomized and sham thymectomized animals had a mild T cell infiltrate with few CD25(+) cells and no anti-donor CTL response in vitro. These results indicate that the thymus is required for rapid and stable induction of tolerance.

Animals↗
PubMed1992

Thymus-independent and thymus-dependent responses to polysaccharide antigens.

Immune responses to polysaccharide antigens are thymus-independent (TI). Conversion of a polysaccharide antigen to a thymus-dependent (TD) antigen by covalent coupling to an immunogenic protein carrier alters the response to the polysaccharide in several important ways. Of primary importance for the prevention of invasive diseases in infants caused by encapsulated bacteria is the shift of the peak antibody response to a much younger age. Another important change is the development of memory B cells primed and ready to respond to either the polysaccharide, as would be encountered during an infection, or to a second dose of the same antigen. Additional immunoglobulin isotypes not seen or seen as a minor component in response to the polysaccharide are also a feature of the TD response. Finally, the diversity of the antibody population is increased after immunization with a TD vaccine compared with that seen after immunization with a TI vaccine.

Animals↗
PubMed1976

Role of the thymus in generation of lymphocyte functions. I. Demonstration of lymphocytes reactive to mitogens and allogeneic cells in the embryonic mouse thymus in organ culture.

The thymuses of 14-day-old CBA mouse embryos cultured for 14 days in organ cultures supplemented with mouse serum contained lymphocytes that were highly reactive to the mitogens concanavalin A (Con A) and leukoagglutinin (LA) and to irradiated allogeneic spleen cells in vitro. In contrast, thymocytes derived from fetal-calf-serum-supplemented organ cultures displayed much weaker responses to the two mitogens and little or no response to the allogeneic spleen cells. Control thymocytes obtained from 1-month-old CBA mice responded well to Con A but not to LA. The responses of these cells to allogeneic spleen cells were delayed compared with the organ-culture-derived cells, which responded promptly, with a maximum already on culture day 2-3. The results demonstrate that the organ culture system provides a convenient model for further study of the generation of immunoreactive cells in the mouse thymus.

Animals↗
PubMed1978

Role of the thymus in generation of lymphocyte functions. III. Further studies of the alloreactivity of lymphocytes developing in mouse thymus organ cultures.

Thymuses of 14-day-old mouse embryos could be maintained in organ culture, using serum-free medium, with generation of lymphocytes that showed strong proliferative reactivity to allogeneic spleen cells in mixed lymphocyte cultures (MLC). Such organ culture derived thymocytes also developed cytotoxic activity against target cells carrying the alloantigens of the stimulating spleen cells in the MLC. The generated cytotoxic activity was, however, proportionately lower than that seen with thymocytes of young mice. A time course study showed that cells with apparent reactivity to both allogeneic spleen cells and to the mitogen Concanavalin A (Con A) first appeared in the thymus organ cultures on day 8-9.

Animals↗
PubMed1984

In vitro induction of specific T cells able to help in the generation of delayed-type hypersensitivity by thymus-dependent and type-II 'thymus-independent' antigens.

An in vitro system is described which supports the primary induction of T cells able to help in the induction of delayed-type hypersensitivity. This system is used to demonstrate that hapten-Ficoll conjugates induce potent hapten-specific T cells with this function. These type-II 'thymus-independent' antigens are thus able to induce specific regulatory T cells. These helper T cells are similar to those induced by classical thymus-dependent antigens in that they are specific for antigen rather than idiotype and act by a linked mechanism.

Animals↗
PubMed1999

Thymus and autoimmunity: production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance.

This study shows that the normal thymus produces immunoregulatory CD25+4+8- thymocytes capable of controlling self-reactive T cells. Transfer of thymocyte suspensions depleted of CD25+4+8- thymocytes, which constitute approximately 5% of steroid-resistant mature CD4+8- thymocytes in normal naive mice, produces various autoimmune diseases in syngeneic athymic nude mice. These CD25+4+8- thymocytes are nonproliferative (anergic) to TCR stimulation in vitro, but potently suppress the proliferation of other CD4+8- or CD4-8+ thymocytes; breakage of their anergic state in vitro by high doses of IL-2 or anti-CD28 Ab simultaneously abrogates their suppressive activity; and transfer of such suppression-abrogated thymocyte suspensions produces autoimmune disease in nude mice. These immunoregulatory CD25+4+8- thymocytes/T cells are functionally distinct from activated CD25+4+ T cells derived from CD25-4+ thymocytes/T cells in that the latter scarcely exhibits suppressive activity in vitro, although both CD25+4+ populations express a similar profile of cell surface markers. Furthermore, the CD25+4+8- thymocytes appear to acquire their anergic and suppressive property through the thymic selection process, since TCR transgenic mice develop similar anergic/suppressive CD25+4+8- thymocytes and CD25+4+ T cells that predominantly express TCRs utilizing endogenous alpha-chains, but RAG-2-deficient TCR transgenic mice do not. These results taken together indicate that anergic/suppressive CD25+4+8- thymocytes and peripheral T cells in normal naive mice may constitute a common T cell lineage functionally and developmentally distinct from other T cells, and that production of this unique immunoregulatory T cell population can be another key function of the thymus in maintaining immunologic self-tolerance.

Animals↗
PubMed1975

Potentiating effect of fetal thymus on fetal liver cells for the promotion of recovery from the radiation injury in murine allogenic radiation chimeras or a little bit of thymus goes a long, long way.

Lethally irradiated CBA (H-2k) mice were treated with small numbers of liver cells from strain-A (H-2a) fetal donors. Recovery from the radiation injury was dependent upon the dose of liver cells administered. Giving very small numbers of fetal thymus cells, in addition to liver cells, had a highly significant and salutary effect on survival. The results suggest that clinical transplantation of liver cells from a single fetus might succeed if thymus cells are added.

Animals↗
PubMed1992

Components of sympathetic innervation of the rat thymus during late fetal and postnatal development: histofluorescence and biochemical study. Sympathetic innervation of the rat thymus.

This study was performed in order to investigate development of sympathetic innervation in the rat thymus. To achieve this aim histofluorescence and biochemical methods were used. The histofluorescence method revealed the presence of sympathetic nervous profiles in this organ for the first time on day 18 of gestation. The density of these profiles and intensity of their fluorescence increased progressively during late embryonal and postnatal development of the organ. In the outer cortex of adult thymus the sympathetic nervous profiles were found mainly in apposition to thymocytes, while in deeper cortex and medulla they were revealed adjacent to thymic epithelial cells. These nervous profiles were also found in close association with thymic autofluorescent cells, which density increased during the thymic postnatal development. Using the fluorometric method the concentrations of neither noradrenaline (NA) and dopamine (DA) nor serotonin (5-HT) were measurable until day 19 of embryogenesis. Their content increased during the postnatal development. The patterns of NA and DA increase during the postnatal development were almost identical, while the pattern of 5-HT increase was quite different. The present results indicate that DA might also be one of the transmitters of the thymic sympathetic nerve supply, as well as that the transmitters of that system can be involved in the regulation of activity of thymic epithelial and autofluorescent cells, but also in the modulation of T cell maturation.

Adrenergic Fibers↗
PubMed1991

Studies of the thymus in Chagas' disease: III. Colonization of the thymus and other lymphoid organs of adult and newborn mice by Trypanosoma cruzi.

Among newborn and adult euthymic and athymic mice infected intraperitoneally with 10(2) or 10(4) trypomastigotes, neonates and adult athymic animals exhibited greater susceptibility with heavier colonization of central and peripheral lymphoid organs. Contiguity was also found to be a significant factor in colonization: after similar inocula, the parasitic load in the thymus was comparable in adults and neonates when the former were infected by subcutaneous injection in the anterior neck. In the nude athymic mice, the Y (reticulotropic) strain and the CL (myotropic) strain exhibited similar invasiveness, suggesting that the host immune response modulated the tissular tropism of these strains seen in the heterozygous littermates (Nu/+). The bone marrow was heavily infected; parasites were found in chondrocytes and cells of the mononucleate phagocytic system. Ultrastructural studies of infected thymus specimens showed that the corticomedullary architecture was unaltered and that both macrophages and epithelial cells were infected: both these cell types were infected in vitro.

Adult↗
PubMed1991

Age-related modification in the thymus of rats and mice: an in vivo study by magnetic resonance. MR imaging of the thymus.

Techniques of magnetic resonance were used to investigate in vivo the normal thymus and its age-related modifications in small rodents. The data were compared with anatomical preparations and histological sections of the animals. The possibility to visualize modifications of the thymus in living organisms open new perspectives for the follow up of experimental manipulations on laboratory animals.

Age Factors↗