Lack of transformation of murine thymocytes by thymic epithelium

Abstract

THE normal thymus consists of two basic components: a reticular–epithelial component derived from the third and fourth bronchial pouches¹ and a lymphoid component from stem cells which migrate into the embryonal thymus from fetal liver² and later from bone marrow³. Two types of thymic reticular cells have been observed by electron microscopy: epithelial reticular cells and mesenchymal reticular cells or macrophages. The villous epithelial cells of the cortex and the cystic epithelial cells of the medulla were shown to be important for T cell differentiation⁴. Cultures of thymus epithelial cells were shown to induce the differentiation of precursor cells into certain mature T lymphocytes^5,6. Recent studies have suggested that thymic epithelium cells (derived from leukaemic thymus) were capable of providing the leukaemogenic signal and thereby inducing in vitro leukaemia transformation of normal thymocytes. Thus, it was claimed that young AKR thymocytes cultured on thymus epithelium monolayers from aged AKR mice could induce leukaemia when injected into normal young recipients⁷. Similarly, monolayers of thymus epithelium cells, derived from radiation leukaemia virus-induced thymomas in C57BL/6 mice could bring about transformation of normal C57BL/6 thymocytes, thereby demonstrating in vitro leukaemogenesis⁸. Our aim here was to study further the possible role of the thymic epithelial reticulum (TER) in leukaemogenesis and we present evidence that the leukaemic cells are not derived from the thymus lymphocytes, nor from a ‘transformation capacity’ of the epithelial cells themselves, but that they are already present within phagocytic TER cells. We used the thymic epithelium monolayer–thymocyte co-cultivation method^7,8 and the transplantation bioassay genotype analysis method⁹ (used to demonstrate the origin of the developing leukaemias following injection of thymocytes or thymic epithelium cells into appropriate recipients).