THYMOCYTES AND RELB-DEPENDENT MEDULLARY EPITHELIAL-CELLS PROVIDE GROWTH-PROMOTING AND ORGANIZATION SIGNALS, RESPECTIVELY, TO THYMIC MEDULLARY STROMAL CELLS

The thymic medulla is composed of distinct epithelial cell subsets, de fined in this report by the reactivity of two novel antibodies, 95 and 29, raised against mouse thymic epithelial cell lines. These antibodi es were used to probe the development of medulla in wild-type or mutan t thymuses. In CD3 epsilon-deficient mice where thymocyte maturation i s arrested at the CD4(-) CD8(-) stage, few scattered 95(+) and 29(+) e pithelial cells are found. When few mature thymocytes develop as in CD 3 zeta/eta mice, expansion and organization of 95(+) but not 29(+) cel ls, becomes detectable. In RelB-deficient mice, T cell maturation proc eeds normally but negative selection is inefficient due to the lack of thymic medulla and dendritic cells. Strikingly, 29(+) epithelial cell s are absent and 95(+) medullary epithelial cells are scattered throug hout the thymus, intermingling with CDR1(+) cortical epithelium. In ch imeric mice lacking only dendritic cells, the corticomedullary junctio n persists and both 95(+) and 29(+) epithelial cells are localized in the medulla. These results suggest that two types of signals are requi red for development of thymic medulla. A growth signal depends upon th e presence of maturing thymocytes, but organization of the thymic medu lla requires the presence of activated 29(+) medullary epithelial cell s.