[Thymic factors influence on melatonin-producing pineal function in mice of different age: the possible mechanisms].

The aging peculiarities of thymic factors influence on pineal gland function in CBA mice were investigated. Significant increase of melatonin serum level in 3 h and decrease in 24 h after one injection of thymic preparation "thymalin" in adult mice was shown. The activating influence of thymalin was depended on season and linked with increase of thymic serum factor (FTS, thymulin) level and decrease of corticosterone blood level. Thymic stroma supernatant of adult mice, which had high level of FTS, intensified in vitro melatonin-producing pineal function. The activating influence of thymic factors in vivo and in vitro on pineal function in old mice was not revealed. FTS content increased and cortocosterone level did not change in old mice after injection of thymalin. The mechanisms of thymic factors influence on melatonin level in adult organism and their peculiarities in aging were discussed.

Establishment of a sensitive radioimmunoassay for serum thymic factor with a special reference to extraction procedures.

A radioimmunoassay (RIA) for serum thymic factor (facteur thymique serique) was established. This assay could detect less than 0.5 pg of serum thymic factor without the interference by other thymic hormones, including thymopoietin II and thymosin alpha 1. Both zinc-free and zinc-bound serum thymic factor showed a similar standard curve, indicating that this RIA could detect both forms of serum thymic factor in the same way. We observed that two procedures were required prior to the measurement in order to measure serum thymic factor content in plasmas; the first, the extraction procedure to remove substances interfering with the assay nonspecifically; the second, the storage of the sample with ethylenediamine tetraacetic acid disodium salt to inhibit the proteases in the plasma to degrade serum thymic factor. By employing this assay system, we observed that cord blood plasmas contained significantly higher level of serum thymic factor than did adult blood plasmas.

A new radioimmunoassay for the thymic peptide thymulin, and its application for measuring thymulin in blood samples.

A new, specific and sensitive radioimmunoassay, using a polyclonal antiserum raised in rabbits, is described for quantitating plasma thymulin. As little as 300 fg thymulin can be measured in one assay tube. The method has been used to measure thymulin in human blood (umbilical vessel blood, 2191 +/- 123 fg/ml; children and adults up to the age of 20 years, 1499 +/- 119 fg/ml; and adults between 21-65 years, 371 +/- 18 fg/ml). There is a highly significant decrease within these three groups (P less than 0.001 by one way analysis of variance). Also plasma thymulin levels were determined in rats (601 +/- 127 fg/ml) and in pooled plasma samples from mice (638 +/- 56 fg/ml). No thymulin was detected in plasma obtained from nude rats, nude mice and thymectomised mice. These results show that the radioimmunoassay described here is a useful quantitative tool for measuring plasma thymulin that will have applications in basic, applied and clinical research.

Thymulin, a zinc-dependent hormone.

Thymulin (formerly called FTS) is a well defined nonapeptide hormone produced by thymic epithelial cells. Its biological activity and antigenicity depend upon the presence of the metal zinc in the molecule. This pharmacologically active metallopeptide induces the differentiation of T-cells and enhances several functions of the various T-cell subsets in normal or partially thymus-deficient recipients. Its effect on suppressor T-cells is, so far, the most remarkable and should be the first to find useful clinical applications. The peptide is a natural hormone, available in synthetic form. It is not toxic and one may foresee its clinical use as one of the major immunoregulatory agents in the near future.

Thymopentin structure and relation to thymic factors.

High-performance liquid chromatography (HPLC) was used to evaluate the purity and batch-to-batch consistency of four commercially available thymic extracts and thymopentin, the synthetic pentapeptide corresponding to the biologically active region of the thymic hormone thymopoietin. The thymus extracts were all extremely heterogeneous, differing one from the other. Additionally, they showed high batch-to-batch variation. In contrast, thymopentin was homogeneous and this homogeneity was consistent in different batches.

Isolation and assay of a human plasma factor affecting human thymus-derived lymphocytes.

An amino acid-containing factor has been isolated from a dialysate of defibrinated human plasma using Sephadex G-25 and Sephadex CM-25 column chromatography. This factor is capable of enhancing "avid" E-rosette formation by normal human lymphocytes, where avid E-rosettes are defined as lymphocytes binding 10 or more sheep red cells. This factor is effective at concentrations as low as 10(-12) g/ml. It resembles the porcine and murine "facteur thymique sérique" (e.g. J.-F. Bach, M. Dardenne, J.-M. Pleau, and J. Rosa, Nature (London) 266, 55, 1977) in its elution characteristics, its capacity to enhance avid E-rosette formation and, tentatively, its amino acid composition.

[From the search for a lymphocytic chalone to the rediscovery of serum thymic factor (FTS)]. / De la recherche d'une chalone lymphocytaire à la redécouverte du facteur thymique sérique (FTS).

Looking for a "lymphocytic chalone" in Bovine spleen extracts, we isolated an immunosuppressive peptide, whose biochemical and biological properties are identical to those of the serum thymic factor FTS. This factor appeared to be a regulator of the humoral immune response.

Characterization of facteur thymique sérique (FTS) in the thymus. II. Direct demonstration of the presence of FTS in thymosin fraction V.

Thymosin fraction V was submitted to the same purification procedure as used for the isolation of the circulating thymic factor (FTS) from pig serum: an FTS-like material was isolated from this fraction and shown to have similar activity, molecular weight, charge and amino acid composition as FTS. These data, together with previous experiments showing the binding of anti-FTS antibodies to reticulo-epithelial cells, provide a direct argument in favour of the presence of FTS in the thymus.

Serum factors modulating in vitro migration of thymus lymphocytes.

Migration of guinea pig thymocytes in sealed glass capillaries was measured in 3 intervals during 24 h of incubation. Two factors present in guinea pig sera which stimulated migration were partly characterized. One factor, with a molecular weight between 10,000 and 100,000 (as judged by ultrafiltration), stimulated migration during the first 2 h of incubation but not later. Only about one third of the sera had this activity. The other factor, which was present in most sera, had a molecular weight exceeding 100,000 and stimulated migration only at later times. Both factors were heat stable and resisted freezing and thawing as well as lyophilization, but were inactivated by storage of sera. Normal human sera stimulated migration from 2 h after start of incubation but, in contrast to guinea pig sera, had a slightly inhibitory effect during the first 2 h. Thymectomy had no effect on guinea pig or human sera as regards ability to modulate migration. Patients with defects in cell mediated immunity did not exhibit any specific alterations in serum activity. However, active disease as well as operations performed on guinea pigs reduced the late stimulatory activity. Additional experiments indicated that migration of thymus cells in glass capillaries depends partly on factors other than cell motility.