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Amplification of the proliferative response to alloantigen by a factor present in an extract of syngeneic thymic lymphoid cells: demonstration of optimal conditions and target cell for factor activity.

A factor extracted from syngeneic thymic lymphoid cells (thymocytes) is shown to amplify the proliferative (MLC) response of syngeneic lymphoid cells to alloantigen in vitro. The optimal conditions for an effect of the thymus factor are quantitatively defined by kinetic and dose-response studies. Other variables that could potentially influence the activity of the thymus factor, such as the presence of 2-mercaptoethanol and the source of alloantigen, are identified. Factor activity can be recovered from semi-allogeneic thymocytes, as well as syngeneic thymocytes. The factor appears to predominantly effect the proliferative response of T cells localized in peripheral lymphoid organs. As such, this factor appears to be distinct from the variety of previously described factors derived from thymic reticuloepithelial elements that are thought to primarily induce the differentiation of T cell precursors found predominantly in bone marrow. Several possible mechanisms of action of this thymocyte-derived factor are considered.

Animals↗

Characterization of autoantibody activities in sera anti-DNA antibody and circulating immune complexes from 12 systemic lupus erythematosus patients.

To examine autoantibodies present in patients with active systemic lupus erythematosus (SLE), sera, circulating immune complexes (CIC), and antibodies purified on DNA-immunoadsorbent were tested by enzyme immunoassay. A panel of self-antigens, including DNA, histones (HIS), glomerular basal membrane (GBM), thymus cell extract (TCE), actin (ACT), myosin (MS), and tubulin (TUB), was used to define their specificities. IgM antibodies against all antigens of the panel were detected in sera, CIC, and in antibodies eluted from the DNA-immunoadsorbent and demonstrated a large polyreactivity. IgG antibodies showed restricted activities against DNA, HIS, GBM, and TCE in sera and a large polyreactivity in CIC. Inhibition experiments were performed to assess their mono- or polyreactivities. Among the IgG autoantibody population recognizing DNA, two populations of IgG antibodies were detected in the sera and in the affinity purified anti-DNA: one recognizes DNA, HIS, and GBM, and the other binds to DNA and to cytoskeletal proteins. These autoantibody populations were found in CIC, which also often contained high amounts of IgG antibodies recognizing ACT and MS. A third population of IgG antibody that recognizes only TCE and could not be inhibited by DNA or other antigens was found in serum and CIC. Our data demonstrate the existence of several populations of autoantibody in serum and CIC of SLE patients: (1) IgM polyreactive autoantibodies, (2) IgG polyreactive autoantibodies recognizing DNA and cytoskeletal proteins, (3) IgG specific to DNA, which cross react with HIS and GBM, and (4) IgG specific to TCE antigens.

Adolescent↗

Detection and localization of autofluorescent substances in thymus tissue of sheep.

An oxygenated sterol was detected by chemical analysis of sheep thymus lipid extracts. It was characterized as 7 beta-hydroxycholesterol, which is well known for its biological activity. Using fluorescence microscopy, attempts were made to correlate this substance to particular histological structures of the thymus tissue. Microscopy revealed an intense yellow-green primary fluorescence distributed throughout the entire thymic parenchyma, which was predominant in the cortico-medullary junction, the vicinity of the Hassall's bodies and the subcapsular space. This indicated an accumulation of the fluorogenic substance in special tissue structures of sheep thymus. This result can be assumed as specific for the thymus, since such primary fluorescence was absent from other simultaneously investigated organs, such as the adrenal.

Aging↗

Effects of the administration of cadmium and zinc on the concentration of zinc in the thymus of rats.

The zinc content of thymus glands of male Wistar rats has been determined during five weeks of treatment with ZnCl2 and CdCl2, and compared with a group of control rats. Thymus gland extracts were chromatographed on columns of Sephadex G-75 and the zinc content of the one hundred fractions obtained were determined by atomic absorption spectrophotometry. The rats treated with ZnCl2 showed an increase in the thymus concentration of zinc bound to high and low molecular weight proteins. The rats treated with CdCl2 showed an increase in zinc concentration, as opposed to the control group, during the first three weeks of treatment, and thereafter show a toxic effect of cadmium on the gland, with ulterior regression of the latter, and a decrease in the concentration of zinc.

Animals↗

Role of a calf thymus preparation in the degradation of native and reductively methylated low density lipoprotein.

1. The clearance of low density lipoprotein (LDL) is mediated by a specific LDL receptor pathway and by an alternative metabolic pathway that is responsible for the receptor-independent LDL catabolism. 2. This alternative catabolism can be studied in vivo using a preparation of chemically modified LDL that are reductively methylated. 3. Recently we showed that a calf thymus protein extract affects the cholesterol metabolism via activation of LDL catabolism. 4. The aim of this study was to investigate whether in vivo the specific LDL receptor pathway and the independent LDL receptor pathway are affected by thymus treatment. 5. The results obtained injecting in rats native and chemically modified 125I-LDL to probe the receptor independent pathway, show that the thymus gland decreases serum cholesterol by activation of the specific LDL receptor pathway. 6. This effect is mainly evident in liver and kidney that represent organs in which the specific LDL receptors are widely present.

Animals↗

Histiocytosis-X.

Twelve of 17 patients with histiocytosis-X were immunologically abnormal, as shown by the presence of circulating lymphocytes spontaneously cytotoxic to cultured human fibroblasts or of antibody to autologous erythrocytes. The patients also had a notable lack of histamine H2 surface receptors on their T lymphocytes, suggesting a suppressor-cell deficiency. The lymphocyte abnormalities were reversed in vitro after incubation in a crude extract of calf thymus gland, and therefore all 17 patients were treated with daily intramuscular injections of this extract. With this therapy, 10 patients entered complete remission -- a response at least as good as that observed in historical controls treated with chemotherapy. A positive clinical response was associated with an increase in the number of T-cell histamine H2 receptors to normal levels and with correction of the other immunologic abnormalities. The results of this preliminary study justify a larger prospective clinical trial of thymic extract and further investigation of the immunoregulatory mechanisms in histiocytosis-X.

Cell Membrane↗

Immunostimulation in recurrent respiratory tract infections therapy in children.

Selected immunologic parameters and effectivity of immunotherapy was evaluated in 117 children (12-month-10-year-1-old) suffering from recurrent respiratory tract infections. All the children displayed a profound depression of T lymphocytes number, which resemble the situation seen in AIDS patients. An increase of serum IgM concentration was also noted. Immunotherapy included treatment with the following preparations: TFX and Levamisol which stimulate T cell functions, Broncho-Vaxom which stimulates specific antibody production and a complex herb preparation PADMA showing undefined general stimulatory activity. Separate group of children was subjected to climatotherapy in Czerniawa Sanatorium and received no immunostimulants. All methods of treatment employed had beneficial effect. The highest percentage of positive results was obtained in children receiving TFX and Levamisol. In all groups under study, an elevation of T cells percentage was observed. This was especially evident in Levamisol treated patients. There was no correlation, however, between T cells number and clinical improvement.

Adjuvants, Immunologic↗