INTESTINAL EPITHELIAL-CELL LINE INDUCTION OF T-CELL DIFFERENTIATION FROM BONE-MARROW PRECURSORS

The mechanism whereby the intestinal microenvironment promotes T cell development in the absence of the thymus is unknown. We show that the murine intestine-derived epithelial cell line, MODE-K, can induce T ce ll differentiation marker expression in vitro on bone marrow (BM) T ce ll precursors. Three-color flow cytometry analysis of T-cell-depleted C3H BM mononuclear cells (MNC) after 4 days of coculture on monolayers of MODE-K indicated that similar to 25% of MNC expressed CD3 and TCR alpha beta. Of these CD3(+) cells, 36% were CD3(lo)CD4(-)CD8(-) double negative (DN), 34% were CD3(lo)CD4(+)CD8 alpha beta(+) double positiv e (DP), and the remainder were CD3(hi)CD4(+)CD8(-) or CD3(hi)CD4(-)CD8 alpha beta(+) single positive (SP). In addition, the T cells which de veloped in coculture with MODE-K expressed the early T cell differenti ation marker CD24 (heat-stable antigen). These T cell subsets did not develop when BM was cocultured with the LTA fibroblast cell line or in medium alone, Interestingly, preventing cell contact between MODE-K a nd BM by culturing in Transwell plates did not interfere with the deve lopment of T cells expressing the DN, DP, or SP phenotypes, Double-pos itive T cells did not develop if splenic MNC were cocultured with MODE -H. These results suggest that the intestinal epithelial environment c an induce and support the T cell development from bone marrow precurso rs. (C) 1996 Academic Press, Inc.