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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-(3)H, 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 (36)sulfate by the thymus, using gel filtration chromatography to isolate soluble macromolecular (35)sulfate-presumed on radioautographic evidence to represent the mucoid epithelial secretory product. Incorporated (35)sulfate 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 (35)sulfate 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.

INCORPORATION OF SULFATE BY THE MOUSE THYMUS: ITS RELATION TO SECRETION BY MEDULLARY EPITHELIAL CELLS AND TO THYMIC LYMPHOPOIESIS