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 cell differentiation marker expression in vitro on bone marrow (BM) T cell 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 approximately 25% of MNC expressed CD3 and TCR alpha beta. Of these CD3+ cells, 36% were CD3loCD4-CD8- double negative (DN), 34% were CD3loCD4+CD8 alpha beta+ double positive (DP), and the remainder were CD3hiCD4+CD8- or CD3hiCD4-CD8 alpha beta+ single positive (SP). In addition, the T cells which developed in coculture with MODE-K expressed the early T cell differentiation marker CD24 (heat-stable antigen). These T cells 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 and BM by culturing in Transwell plates did not interfere with the development of T cells expressing the DN, DP, or SP phenotypes. Double-positive T cells did not develop if splenic MNC were cocultured with MODE-K. These results suggest that the intestinal epithelial environment can induce and support the T cell development from bone marrow precursors.
Maric
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Intestinal Disease Research Programme, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Kaiserlian
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Croitoru
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D000818:Animals; D001853:Bone Marrow / Q000276:immunology*; D001854:Bone Marrow Cells; D017252:CD3 Complex / Q000096:biosynthesis; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D018920:Coculture Techniques; D004847:Epithelial Cells; D004848:Epithelium / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology*; D007413:Intestinal Mucosa / Q000166:cytology* / Q000276:immunology*; D008212:Lymphocyte Depletion; D051379:Mice; D008809:Mice, Inbred C3H; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*
D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens