Incorporation of Sulfate by the Mouse Thymus: Its Relation to Secretion by Medullary Epithelial Cells and to Thymic Lymphopoiesis

Abstract

The thymus was examined in suckling mice during normal development and the involution and regeneration produced by injection of cortisol, in experiments designed to test the hypothesis that medullary epithelial cells secrete a ymphopoietic hormone responsible for controlling the magnitude of thymic lymphopoiesis. Cellular events were observed by light and electron microscopy. Lymphopoiesis was assessed, after injection of thymidine-3H, by counting the proportion of lymphocytes labeled in radioautographs of thymus. Cortical lymphopoiesis was distributed heterogeneously, being concentrated in the subcapsular region, but medullary lymphopoiesis was statistically homogeneous in distribution and similar in magnitude to the average level of cortical lymphopoiesis in suckling mice. Therefore counts of the labeling index in the medulla were used to estimate the size of the proliferating population of lymphocytes. Epithelial secretory activity was estimated by measuring the incorporation of 36sulfate by the thymus, using gel filtration chromatography to isolate soluble macromolecular 35sulfate—presumed on radioautographic evidence to represent the mucoid epithelial secretory product. Incorporated 35sulfate accumulated rapidly for 4 hr, reached a peak at 12 hr, and had fallen to half that level by 24 hr after a single injection—as would be expected of a secretory product. During normal postnatal development the size of the proliferating population of lymphocytes and the magnitude of 35sulfate incorporation increased in parallel. During acute involution induced by cortisol both parameters diminished greatly but rose to high levels during subsequent regeneration. Accordingly, lymphopoiesis and sulfate incorporation —as defined and measured in these experiments—correlated linearly over a wide range of variation, providing circumstantial evidence to support the hypothesis that medullary epithelial cells secrete a sulfated mucoid lymphopoietic hormone. This conclusion is discussed in terms of the roles of thymus and adrenal cortex in development of the lymphoid system and maturation of immunological competence.

Cloned mouse cells with natural killer function and cloned suppressor T cells express ultrastructural and biochemical features not shared by cloned inducer T cells.

“…In contrast to our cloned cell lines, which have been analyzed in detail, the distribution of sulfated glycosaminoglycans among lymphocyte populations in vivo is poorly understood. Earlier work detected little ~5SO4 incorporation by mouse thymic (43) or guinea pig peripheral blood (19) lymphocytes; however, these studies were performed with uncloned leukocytes containing undefined but probably minor numbers of NK cells or cytolytic/suppressor T ceils. At the present time, guinea pig (19) and human basophils (44,45) and guinea pig Kurloff cells (19,46) represent the only circulating leukocytes known to contain high concentrations of granule-associated chondroitin sulfates.…”

Effect of sex hormones on the thymus and lymphoid tissue of ovariectomized rats

“…1) How do various types of sex steroids alter the histology of the thym us w ith regard to the proliferation and destruction of thym ic lymphocytes, and how may these, in tu rn , affect the population of lym phocytes in the general circulation and in other lymphoid tissue? 2) Docs the injection of sex steroids produce any delectable changes in cellular stru ctu re and population dynam ics of thym ic epithelial reticular cells, w hich arc nominally the prime candidates for the production and secretion of thym ic lym phopoietic factor [Clark, 1968] ? 3) Since the adm inistration of sex steroids into experim ental anim als can alter the synthesis and release of adrenal glucocorticoid hormones [Kitay, 1963], it can be asked w hether the apparent thym ic suppressive action of sex steroids is m ediated by the level of glucocorticoids, or w hether sex steroids themselves possess direct action.…”

Ultrastructure of Epithelial Thymic Cysts of the Chicks

“…These cells can incorporate labelled glucosamine (Clark, 1968), secrete periodic acid Schiff reaction (PAS) positive material (Mandel, 1968;Pfoch, 1971), and are the probable site of production of lymphopoietic factor (Clark, 1966;Rusu et ai, 1981) or glycosaminoglycan product which can "cover-up" cell surface antigens in the maturing thymocytes (Higley and O'Morchoe, 1984). The immunological deficiency in the "Nude" mouse may be attributed to the absence of the cystic cells (Cordier, 1974).…”