thymalfasin and Myasthenia-Gravis

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

Topics: Arthritis, Rheumatoid; Autoimmune Diseases; Cytotoxicity, Immunologic; Humans; Lupus Erythematosus, Systemic; Lymphocyte Culture Test, Mixed; Lymphocytes; Myasthenia Gravis; Thymalfasin; Thymosin; Thymus Gland; Thymus Hormones

Thymosin alpha 1 (alpha 1) is a potent thymic polypeptide hormone. With antibodies against synthetic thymosin alpha 1, indirect immunofluorescence was applied to human normal thymus and to hyperplastic, thymomatous or "involuted" thymus of myasthenia gravis (MG) patients. Alpha 1 was localized only in the epithelial cells, lying singly, grouped, in Hassall's corpuscles or proliferated in thymomas. In contrast to normal thymus, which had fewer and more weakly stained cells, MG hyperplastic thymus had many strongly positive epithelial cells: this was markedly evident in thymomas. "Involuted" MG thymus had a few but brightly stained cells lying within the fatty tissue. In tissue cultures of human thymus, anti-alpha 1 stained the epithelial cells, but not fibroblasts. These findings: (a) demonstrate the origin of the thymic hormone alpha 1 to be the thymic epithelial cell; (b) raise the possibility that excess alpha 1 may act pathologically to facilitate and perpetuate the dysimmune mechanism in MG; (c) may partially explain the beneficial effect of thymectomy in MG patients of any age; and (d) suggest that epithelial cells may be autonomous for the production of alpha 1 as evidenced by their positivity in tissue culture.

Topics: Adolescent; Adult; Child; Epithelium; Fluorescent Antibody Technique; Humans; Middle Aged; Myasthenia Gravis; Thymalfasin; Thymoma; Thymosin; Thymus Gland; Thymus Hormones; Thymus Hyperplasia; Thymus Neoplasms

Thymosin-alpha 1 (alpha 1) is a potent thymic polypeptide hormone. Using anti-alpha 1 antibodies, we applied indirect immunofluorescence to human normal thymus of different ages and to hyperplastic, thymomatous, and "involuted" thymus of myasthenia gravis (MG) patients. Alpha 1 was localized only in the epithelial cells, lying singly, grouped, in Hassell's corpuscles, and proliferated in thymomas. Whereas normal thymuses and fewer and weakly stained cells, MG thymuses had many strongly positive epithelial cells; this was more evident in thymomas. Germinal centers were unstained. "Involuted" MG thymuses had small islands of brightly stained cells lying among the fatty tissue. In cultured thymuses from three MG patients, epithelial cells but not fibroblasts were brightly stained for alpha 1. Our findings (a) demonstrate the location, and presumably the origin, of alpha 1 to be the thymic epithelial cell; (b) suggest the possibility that excess alpha 1, because of its known effect on T-lymphocyte maturation and transformation of precursors to helper T-cells, may act pathologically to facilitate and perpetuate the dysimmune mechanism in MG; (c) may partially explain the beneficial effect of thymectomy in MG patients of any age; and (d) indicate that epithelial cells may be autonomous for the production of alpha 1 as evidenced by their alpha 1 positivity in culture.

Topics: Adolescent; Adult; Cells, Cultured; Epithelium; Fluorescent Antibody Technique; Humans; Middle Aged; Myasthenia Gravis; T-Lymphocytes; Thymalfasin; Thymosin; Thymus Gland; Thymus Hormones