thymic-factor--circulating and Thymoma

This paper reviews the mechanism of sex hormone actions on the thymus, presenting mainly our data obtained at the cellular and molecular levels. First, data supporting the "genomic" action via the nuclear sex hormone receptor complexes are as follows: 1) sex hormone receptors and the thymic factor (thymulin) are co-localized in thymic epithelial cells, but not in T cells; 2) production/expression of thymic factors (thymulin, thymosin alpha 1) are remarkably inhibited by sex hormone treatment; 3) sex hormones cause changes in T cell subpopulations in the thymus; and 4) sex hormones strongly influence the development of thymus tumors in spontaneous thymoma BUF/Mna rats through their receptor within the tumor cells. Secondly, data indicating the "non-genomic" action of sex hormones via a membrane signal-generating mechanism are as follows: 1) the proliferation/maturation of thymic epithelial cells is mediated through protein kinase C activity introduced by sex hormones; 2) sex hormones directly influence DNA synthesis and cdc2 kinase (cell cycle-promoting factor) activity.

Topics: Animals; Castration; Cell Division; Cells, Cultured; Estrogens; Female; Immunohistochemistry; Lymphocyte Subsets; Male; Mice; Mice, Inbred C57BL; Microscopy, Immunoelectron; Rats; Receptors, Estrogen; Sex Factors; Thymic Factor, Circulating; Thymoma; Thymus Gland

Benign thymic hyperplasia (TH) is a known feature of hyperthyroidism. In most cases, thymic enlargement is minimal; however, this syndrome may occasionally appear as an appreciable anterior mediastinal mass. Recognition of the benign nature of TH and its regression following treatment of the hyperthyroidism is important to prevent unnecessary surgical procedures. We present a case of TH associated with hyperthyroidism due to Graves' disease.

Topics: Animals; Antithyroid Agents; Diagnosis, Differential; Female; Graves Disease; Humans; Hyperplasia; Immunoglobulins, Thyroid-Stimulating; Indium Radioisotopes; Magnetic Resonance Imaging; Mediastinal Neoplasms; Methimazole; Radionuclide Imaging; Receptors, Thyrotropin; Somatostatin; Thymic Factor, Circulating; Thymoma; Thymus Gland; Thymus Neoplasms; Young Adult

Different age-related immune pathogenetic mechanisms in myasthenia gravis (MG) have been suggested because of restoration after thymectomy (Tx) of altered zinc, thymulin (TH) and T-cell subsets exclusively in early-onset patients (younger <50 years), not in late-onset patients (older >50 years). In this context interleukin-2 (IL-2), interleukin-6 (IL-6) and thymoma are crucial because both involved in MG pathogenesis and correlated with acetylcholine receptors (AchRs) Ab production. Moreover, IL-2 and IL-6 are zinc-dependent, are altered in aging and related with zinc and TH age-dependent declines. Moreover, zinc is relevant for immune efficiency. In order to confirm these different age-related pathogenetic mechanisms further, the role of thymoma, zinc, TH, IL-2 and IL-6 is studied in MG patients with generalized MG with and without thymoma before and 1 month and 1 year after Tx. The high IL-2, IL-6, zinc, and AChR Ab levels observed before Tx are significantly correlated each other in younger MG patients (<50 years) independently by thymoma and in older MG patients (>50 years) with thymoma. No correlations exist in older MG patients without thymoma. Thymulin is not correlated with other parameters considered to be both in younger and older MG patients independently by the thymoma. Thymectomy restores zinc; immune parameters and AChR Ab are exclusively in the younger group, not in the older one. These findings suggest that IL-2 and IL-6, via zinc, rather than TH, may be involved in different age-related pathogenetic mechanisms mainly in early-onset MG. By contrast, thymoma may be involved in MG etiology in late-onset representing, as such, a useful discriminant tool for MG etiology between early and late-onset MG patients. Because autoimmune phenomena may rise in aging, a parallelism with altered immune functions during aging is discussed.

Topics: Adolescent; Adult; Aged; Aging; Female; Humans; Interleukin-2; Interleukin-6; Male; Middle Aged; Myasthenia Gravis; Receptors, Cholinergic; Thymectomy; Thymic Factor, Circulating; Thymoma; Thymus Neoplasms; Time Factors; Zinc

This study of a particular case of tumor posed and resolved problems of differential diagnosis between an undifferentiated tumor and a thymoma by using electron microscopy in association with immunocytochemical methods. The first step was the distinction between an epithelial and a mesenchymal tumor, which was done by electron microscopy and immunofluorescence observation with anti-keratin antibody. The second step, a new approach to this problem, was the distinction between an epithelial tumor of thymic origin and another tumor located in the mediastinal lodge. A clear distinction was made by observation in immunofluorescence using anti-thymulin monoclonal antibody. This double approach permits differential diagnosis, excludes neoplasms of germ-cell origin, malignant lymphomas and leukemias, as well as mesenchymal tumors, and affirms the thymic origin of the tumor observed. A second type of cell observed in this tumor with a peculiar aspect, different from all types of epithelial cells observed in normal thymus, is discussed.

Topics: Diagnosis, Differential; Epithelium; Fluorescent Antibody Technique; Humans; Immunohistochemistry; Male; Microscopy, Electron; Middle Aged; Thymic Factor, Circulating; Thymoma; Thymus Gland; Thymus Neoplasms

We investigated by an immunofluorescence assay the presence of the P19 antigen in cultures of human thymic epithelial cells (HTEC). This antigen is acquired during human thymic ontogeny, and in infants and adults most thymic epithelial cells were shown to display P19 antigen. In cultures of normal human thymic epithelium, we observed that the P19 protein was less expressed than in situ. However, the percentage of P19-containing cells increased with culture age, a finding which could be compared to that obtained recently concerning immunodetection of thymulin-containing cells. Indeed, thymic epithelial cells keep their endocrine function in culture and the number of thymulin-positive cells increases as a function of time. Interestingly, the increase of P19 expression was generally parallel to that of thymulin production. These data may reflect functional modifications of the cells in relation to differentiative effects. Similar results were obtained in pathological thymuses described as hyperplasia in M G patients. In contrast, thymomas behaved differently. Among the three benign thymomas tested, two were consistently P19-negative or faintly stained in culture conditions while one was very brightly stained from the onset and remained P19-positive throughout the culture; this finding correlates with studies on frozen sections. Our data show modifications of P19 antigen expression both in culture and in thymomas and suggest that P19 synthesis may be dependent upon components (factors or cells) which are efficient in the thymic microenvironment but partially defective in the cultures or after neoplastic transformation.

Topics: Antigens, Surface; Cells, Cultured; Epithelium; Fluorescent Antibody Technique; Humans; Myasthenia Gravis; Thymic Factor, Circulating; Thymoma; Thymus Gland; Thymus Hyperplasia; Thymus Neoplasms

Using an immunofluorescence (IF) assay, the presence of metallothionein (MT) was investigated in sections of normal and pathologic human thymuses as well as in cultures of thymic epithelial cells. This protein, known to have a high binding affinity for class II B transitional metals, such as zinc, was detected in the epithelial component of the thymus. Moreover, double labeling experiments with the anti-MT and an anti-thymulin monoclonal antibody showed that all cells containing thymulin, a thymic hormone whose active structure is known to contain zinc, also exhibited large amounts of metallothionein. These results, together with the fact that zinc and thymulin have been detected in the same type of cell organelles, lead to the conclusion that the MT present in thymic epithelial cells might be involved in the mechanism of zinc storage in these cells, thus favoring the secretion of thymulin in its biologically active, zinc-containing form.

Topics: Animals; Biological Assay; Child, Preschool; Cross Reactions; Fluorescent Antibody Technique; Humans; Immune Sera; Infant; Metallothionein; Mice; Mice, Inbred C57BL; Thymic Factor, Circulating; Thymoma; Thymus Gland; Thymus Hormones; Thymus Neoplasms; Zinc

The localization of the three best-defined thymic hormones, namely, thymulin, thymopoietin and thymosin alpha 1 was studied by immunofluorescence using antibodies directed against these three molecules. With both human thymus frozen sections and cultured cells, thymic hormones were found exclusively in the epithelial component (recognized by its keratin content), in normal as well as pathological thymuses. The double-labeling experiments using the different anti-thymic hormone antibodies showed that the same epithelial cells contained the three hormones. These results suggest that the production of different hormones in the thymus is accomplished by the same epithelial cells.

Topics: Cells, Cultured; Fluorescent Antibody Technique; Freezing; Histological Techniques; Humans; Myasthenia Gravis; Thymalfasin; Thymic Factor, Circulating; Thymoma; Thymopoietins; Thymosin; Thymus Gland; Thymus Hormones; Thymus Hyperplasia; Thymus Neoplasms

A 78-yr-old patient presented with a malignant thymoma with a predominance of epithelial cells. Lymphocyte markers (E rosettes, T-cell-specific xenoantigen and surface Ig) and electrophoretic studies showed that more than 95% of the peripheral blood lymphocytes were T cells. High levels of circulating thymic factor were repeatedly found before treatment (irradiation and chemotherapy). It is suggested that inappropriate hypersecretion of thymic hormone is responsible or can contribute to the immunological abnormalities found in this patient.

Topics: Aged; Drug Therapy, Combination; Humans; Lymphocyte Activation; Male; Rosette Formation; T-Lymphocytes; Thymic Factor, Circulating; Thymoma; Thymus Hormones; Thymus Neoplasms