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PubMed1974

Induction of T-cell differentiation in vitro by thymin, a purified polypeptide hormone of the thymus.

Thymin, a purified polypeptide isolated from bovine thymus, was shown to induce the expression of differentiation antigens characteristic of thymocytes [TL and Thy-1 (theta)] when incubated in vitro with mouse bone marrow or spleen cells. This induction occurred in 5-10% of the cells from bone marrow after a 2-hr incubation with subnanogram concentrations of thymin. The induced cells expressed more TL and Thy-1 (theta) antigens than average normal thymocytes.

Animals↗
PubMed1990

Cellular levels of thymosin immunoreactive peptides are linked to proliferative events: evidence for a nuclear site of action.

Thymosin alpha 1 (T alpha 1), the N-terminal 28-amino acid fragment of prothymosin alpha (ProT alpha), and ProT alpha, although originally isolated from whole thymus extracts, are also present in nonthymic cells and tissues. We used an ELISA with an antibody raised against T alpha 1 to investigate the relationship between intracellular levels of thymosin immunoreactive peptide(s) (TIP) and cell proliferation in a rat small intestinal IEC-6 cell line. Increasing TIP levels were observed during cell proliferation, which decreased when proliferation was halted by cellular contact inhibition. Serum feeding of cells previously rendered quiescent by serum starvation resulted in a significant increase in TIP within 1 hr. Conversely, serum starvation decreased TIP levels within 1 hr. Peak TIP levels appeared after 3 hr of serum incubation, while maximum [3H]thymidine incorporation was noted after 9 hr, suggesting maximum TIP concentrations in the G1 phase of the proliferative cycle. Immunoelectron microscopy demonstrated an association of TIP with condensed nuclear chromatin. These results support a relation of intracellular TIP levels to IEC-6 cell proliferation and also a nuclear site of action. HPLC analysis of cellular homogenates from proliferating IEC-6 cells revealed a peak of immune reactivity that elutes in the position of T alpha 1.

Animals↗
PubMed2004

Functional assessment of alphaEbeta7/E-cadherin interactions in the steady state postnatal thymus.

T cell differentiation in the thymus depends on sequential interactions between lymphoid progenitors and stromal cells in discrete regions of the cortex. Here, we show that despite alphaEbeta7 expression by a subset of the earliest intrathymic precursors (and E-cadherin expression by thymic stroma), interaction of these elements is not required for proper localization of early progenitors into the cortex, or for successful steady state differentiation. These findings indicate that despite in vitro data demonstrating alphaEbeta7 mediated adhesion and proliferation of intrathymic T cell precursor populations, T lymphocyte development can proceed independently of alphaEbeta7/E-cadherin interactions.

Animals↗
PubMed1981

Lyt-2 and lyt-3 antigens are on two different polypeptide subunits linked by disulfide bonds. Relationship of subunits to T cell cytolytic activity.

Lyt-2 and Lyt-3 antigens are carried on separate disulfide-bonded subunits of the same cell surface macromolecules. These are present on thymocytes in a variety of multimeric forms consisting of disulfide-bonded dimers, tetramers, and hexamers of pairwise combinations of three subunits (30,000, 34,000, and 38,000 Mr). From reduced and alkylated Nonidet-P40 thymus extracts, a monoclonal anti-Lyt-3 precipitates only the 30,000 Mr subunit, but not the 30,000 Mr subunit. Almost all of the Lyt-2 and Lyt-3 subunits on the cell are covalently linked by disulfide bonds. However, small amounts of free Lyt-3 subunit was seen in some experiments. Similarly, small amounts of Lyt-2-3- material, consisting of dimers of the 38,000 and 34,000 Mr subunits were identified. Each of the three subunits migrated with a basic charge (pI greater than 8) on two-dimensional gels. Cytotoxic effector cells that are blocked by anti-Lyt-2 and anti-3 can be treated with trypsin and other arginine-specific proteases to remove these antigens. At low concentrations of these proteases, Lyt-3 antigens are selectively removed. After selective removal of Lyt-3 antigens, cytotoxic effector cells are still active and blocking of activity by anti-Lyt-3 is significantly reduced, whereas blocking of activity by anti-Lyt-2 is significantly increased. Neither Lyt-2 nor Lyt-3 is allelically excluded on thymocytes or T cells. These results suggested that the Lyt-2, Lyt-3 macromolecules are associated with but do not serve as the T cell antigen receptor.

Animals↗
PubMed1992

Disseminated Langerhans cell histiocytosis in identical twins unresponsive to recombinant human alpha-interferon and total body irradiation.

Monozygotic twin boys presented at 1 year of age with seborrheic skin rash, otorrhea, and hepatosplenomegaly. Skin biopsy confirmed Langerhans cell histiocytosis. Treatment with conventional antineoplastic drugs and with calf thymus extract was ineffective. The disease remained refractory to recombinant human alpha-interferon and to low-dose total body irradiation, and the children died between 3 and 3 1/2 years of age.

Combined Modality Therapy↗
PubMed1995

Antibodies to small ribonucleoprotein and to 73-kD heat shock protein: two distinct markers of mixed connective tissue disease.

We set out to discover whether antibodies to small ribonucleoprotein antigens (RNP) and to 73-kD heat shock protein (hsp 73) which have been proposed as markers of mixed connective tissue disease (MCTD) recognize different epitopes. MCTD serum was immunoadsorbed on hsp 73-coupled Sepharose and the affinity retained, and non-retained fractions were checked by immunoblotting for recognition of either purified bovine hsp 73 or calf thymus extract RNPs. The hsp 73 affinity-bound serum fraction recognized hsp 73 but not RNP antigens, the reverse being true for the non-retained fraction. We conclude that anti-hsp 73 and anti-RNPs are distinct markers of MCTD.

Antigens, Nuclear↗
PubMed1977

Thymic microenvironment: selective activities of soluble and insoluble components.

Two components of the thymic microenvironment have been separated, and their biological properties have been studied. The first component, soluble thymic factor (STF), after injection into syngeneic recipients, provoked a temporary decrease in thymic weight on day 7, concomitant with an increase in the level of T cells in lymph nodes (but not in the spleen), followed by a general hypertrophy of lymph nodes peaking on day 21. In contrast, after the injection of the second component, insoluble thymic fraction (ITF), there was an increase in the number of prothymocytes in the thymic subcapsulary cortex, followed by general thymic hypertrophy on days 14 and 21. STF is believed to trigger a selective migration of lymph-node-seeking T cells from the thymus, whereas ITF seems to play a role in the differentiation step preceding that imparted by STF.

Animals↗
PubMed1975

Influence of thymectomy, transfer of thymus and bone marrow cells and treatment with thymosin on the depressed splenic release of lymphocytes into the blood after irradiation.

The content of lymphocytes in blood samples from the splenic vein and the splenic artery of guinea pigs was determined and the veno-arterial difference in number of cells was used as measure of the net release of cells from the spleen into the blood. The splenic release of lymphocytes was reduced after whole body irradiation with 300 rad. This reduction could partly be prevented by transfusion of bone marrow cells after irradiation, 10(6) cells being the most effective dose. In thymectomized, irradiated animals the restoration of the splenic release of lymphocytes after irradiation was impaired in comparison with sham-operated animals. In the thymectomized animals the transfusion of 10(6) thymus cells had a restitutive effect on the splenic release of lymphocytes, while transfusion of bone marrow cells or daily treatments with thymosin, alone or combined with transfusion of bone marrow cells, had no such restitutive effect. The results indicate that restoration of the splenic release of lymphocytes into the blood after irradiation is thymus dependent and probably caused by a traffic of lymphocytes from the thymus to the spleen.

Animals↗
PubMed1975

Thymosin-induced differentiation of murine thymocytes in allogeneic mixed lymphocyte cultures.

Calf thymosin is shown to enhance the one-way MLR of CBA thymocytes cultured with allogeneic mitomycin-C- treated C57BL/J6 spleen cells. Thymosin does not enhance the one-way MLR of CBA thymocytes cultured with syngeneic mitomucin-C-treated spleen cells. Based on this finding we present a relatively simple, rapid and quantitative in vitro microculture hioassay for inducers of T-cell differentiation and propose that thymosin treatment, when accompanied by antigen presentation, induces the two-step maturational sequence of pre-T yields T1 yields T2.

Animals↗