Inhibition of thymocyte mitogenic responses by coculture with thymic epithelial cells

We have previously reported the isolation and culture of two morphologically distinct types of murine thymic epithelial cells (TECL and TECs) and have studied their capacity to produce soluble factors as well as to bind thymocytes in vitro. In the present study, we examined whether direct interactions of thymic epithelial cells with thymocytes regulate thymocyte function by studying the effect of these thymic epithelial cell lines on thymocyte responses to mitogen. We found that direct contact between thymocytes and epithelial cells markedly suppresses both thymocyte and splenocyte responses to mitogen. This effect is irreversible after a 24-hr incubation on thymic epithelial cells, is not H-2 restricted, and appears to be epithelial cell specific. The inhibitory effect is mediated by a molecule or molecules present constitutively on the plasma membrane of epithelial cells. One mechanism of inhibition involves the generation of suppressor cells on contact of thymocytes with thymic epithelial cells or cell membranes. However, it is also possible that molecules with direct immunosuppressive activity may be present on these cell membranes.