title: Positive selection of gamma delta CTL by TL antigen expressed in the thymus.
abstract: To elucidate the funciton of the mouse TL antigen in the thymus, we have derived two TL transgenic mouse strains by introducing Tl alpha 2-3 of A strain origin with its own promoter onto a C3H background with no expression of TL in the thymus. These transgenic mouse strains, both of which express high levels of Tla2-3-TL antigen in their thymus, were analyzed for their T cell function with emphasis on cytotoxic T lymphocyte (CTL) generation. A T cell response against TL was induced in Tg. Tla2-3-1, Tg. Tla2-3-2, and control C3H mice by skin grafts from H-2Kb/T3b transgenic mice, Tg.Con.3-1, expressing T3b-TL ubiquitously. Spleen cells from mice that had rejected the T3b-TL positive skin grafts were restimulated in vitro with Tg. Con.3-1 irradiated spleen cells. In mixed lymphocyte cultures (MLC), approximately 20% and 15% of Thy-1+ T cells derived from Tg.Tla2-3-1 and Tg.Tla2-3-2, respectively, expressed TCR gamma delta, whereas almost all those from C3H expressed TCR alpha beta. The MLC from Tg. Tla2-3-2 and C3H demonstrated high CTL activity against TL, while those from Tg. Tla2-3-1 had little or none. The generation of gamma delta CTL recognizing TL in Tg. Tla2-3-2, but not C3H mice, was confirmed by the establishment of CTL clones. A total of 14 gamma delta CTL clones were established from Tg. Tla2-3-2, whereas none were obtained from C3H. Of the 14 gamma delta CTL clones, 8 were CD8+ and 6 were CD4-CD8- double negative. The CTL activity of all these clones was TL specific and inhibited by anti-TL, but not by anti-H-2 antibodies, demonstrating that they recognize TL directly without antigen presentation by H-2. The CTL activity was blocked by antibodies to TCR gamma delta and CD3, and also by antibodies to CD 8 alpha and CD8 beta in CD8+ clones, showing that the activity was mediated by TCR gamma delta and coreceptors. The thymic origin of these gamma delta CTL clones was indicated by the expression of Thy-1 and Ly-1 (CD5), and also CD8 alpha beta heterodimers in CD8+ clones on their surfaces and by the usage of TCR V gamma 4 chains in 12 of the 14 clones. Taken together, these results suggest that Tla2-3-TL antigen expressed in the thymus engages in positive selection of a sizable population of gamma delta T cells.
authors.affiliation: Laboratory of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tsujimura
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.forename: A
authors.initials: A
authors.lastname: Morita
authors.forename: H
authors.initials: H
authors.lastname: Hasegawa-Nishiwaki
authors.forename: S
authors.initials: S
authors.lastname: Iwase
authors.forename: Y
authors.initials: Y
authors.lastname: Obata
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016827:CD8 Antigens / Q000096:biosynthesis; D002999:Clone Cells; D006084:Graft Rejection / Q000276:immunology; D007111:Immunity, Cellular; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D017710:Lymphocyte Transfusion; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis; D017386:Sequence Homology, Amino Acid; D016038:Skin Transplantation / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
chemical_list: D016827:CD8 Antigens; D008562:Membrane Glycoproteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; C028388:thymus-leukemia antigens