Murine nursing thymic epithelial cell lines capable of inducing thymocyte apoptosis express the self-superantigen Mls-1a.
Two cloned thymic epithelial cell (TEC) lines, D2.TEC-A3 and AKR TEC-K1, were established from minor lymphocyte-stimulating (Mls)-1a-positive normal, 4-week-old DBA/2 (H-2d, Mls-1a2a) mice and AKR (H-2k, Mls-1a2b) mice, respectively. Both cell lines were MHC class I and class II (both I-A and I-E) positive without stimulation by interferon-gamma. They were capable of infolding immature thymocytes to form thymic nurse cells (TNC; we call this type of TEC "nursing TEC") and induced apoptosis with DNA fragmentation in immature thymocytes. Using a primary Mls mixed lymphocyte reaction (MLR) we demonstrated that self-superantigen Mls-1a was expressed on these cloned nursing TEC lines. D2.TEC-A3 cells stimulated nylon-wool-purified splenic T cells obtained from H-2d-compatible BALB/c (Mls-1b2a) and B10.D2 (Mls-1b2b) mice with a maximal response at a stimulator:responder ratio of 1:40 after 4 days of the coculture. AKR TEC-K1 cells also stimulated purified T cells from H-2k-compatible C3H/He mice (Mls-1b2a) in a similar manner. The Mls MLR induced by the nursing TEC lines was completely inhibited in the presence of anti-mouse I-A and anti-mouse I-E monoclonal antibodies. These results suggest that nursing TEC/TNC could be involved in negative selection due to apoptosis.
Department of Immunology and Immunopathology, Kagawa Medical School, Japan.
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Hiramine
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Nakagawa
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Hojo
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D002460:Cell Line; D004587:Electrophoresis, Agar Gel; D004848:Epithelium / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D016747:Minor Lymphocyte Stimulatory Antigens / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology* / Q000648:ultrastructure
D016747:Minor Lymphocyte Stimulatory Antigens