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.