Abstract

DEVELOPMENT of the mammalian lymphoid system and attainment of full immunocompetence have been shown to depend on the presence of the thymus during early life1–3. The possibility has been considered that the multiple functions of the neonatal thymus are effected not only by migration of viable thymocytes or cells preformed elsewhere which become competent within the environment of the thymus, but also by means of a diffusible substance secreted by the thymus and affecting differentiation of lymphocytic cells outside this organ. Evidence for such a humoral mechanism has accumulated from studies of the ability of thymic tissue contained within cell-tight diffusion chambers to prevent the deficiencies resulting from surgical removal of the thymus. Specifically, mice implanted intraperitoneally with chambers allowing passage of fluids but not of intact cells showed neither depletion of lymphocytes of peripheral blood and lymphoid organs nor characteristics of the wasting syndrome which follows thymectomy of newborn animals4. Furthermore, the ability to form antibodies in a primary response against sheep erythrocytes was, to a large extent, maintained5, as was the capacity of neonatally thymectomized mice to reject skin homografts6. The non-cellular nature of this thymic substance has been confirmed by studies of the restorative effects of a cell-free component extracted from thymus of xenogeneic species. In neonatally thymectomized mice, wasting disease was prevented and the normal lymphocyte population of peripheral blood and spleen was maintained by injection of such extracts7,8. Furthermore, the abilities of such mice to reject both skin grafts and tumours were partially restored and graft versus host reactivity was partly returned to the spleen cells of thymectomized mice by calf thymus extracts9,10.

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