J. Exp. Med.
© The Rockefeller University Press
0022-1007/96/12/2175/10 $2.00
Volume 184 December 1996 2175-2184

Positive Selection of CTL by TL Antigen Expressed in the Thymus

By Kunio Tsujimura,^* Toshitada Takahashi,^* Akimichi Morita,^* Hitomi Hasegawa-Nishiwaki,^* Shigeru Iwase,^*§ and Yuichi Obata^*

From the ^* Laboratory of Immunology, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya 464, Japan;  Department of Dermatology, Nagoya City University School of Medicine, Mizuho-ku, Nagoya 467, Japan; and ^§ Department of Chemical Hygiene and Nutrition, Faculty of Pharmaceutical Sciences, Nagoya City University, Mizuho-ku, Nagoya 467, Japan

To elucidate the function of the mouse TL antigen in the thymus, we have derived two TL transgenic mouse strains by introducing Tla^a-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 Tla^a-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.Tla^a-3-1, Tg.Tla^a-3-2, and control C3H mice by skin grafts from H-2K^b/T3^b transgenic mice, Tg.Con.3-1, expressing T3^b-TL ubiquitously. Spleen cells from mice that had rejected the T3^b-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.Tla^a-3-1 and Tg.Tla^a-3-2, respectively, expressed TCR, whereas almost all those from C3H expressed TCR. The MLC from Tg.Tla^a-3-2 and C3H demonstrated high CTL activity against TL, while those from Tg.Tla^a-3-1 had little or none. The generation of CTL recognizing TL in Tg.Tla^a-3-2, but not C3H mice, was confirmed by the establishment of CTL clones. A total of 14  CTL clones were established from Tg.Tla^a-3-2, whereas none were obtained from C3H. Of the 14  CTL clones, 8 were CD8⁺ and 6 were CD4CD8 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 and CD3, and also by antibodies to CD8 and CD8 in CD8⁺ clones, showing that the activity was mediated by TCR and coreceptors. The thymic origin of these CTL clones was indicated by the expression of Thy-1 and Ly-1 (CD5), and also CD8 heterodimers in CD8⁺ clones on their surfaces and by the usage of TCR V4 chains in 12 of the 14 clones. Taken together, these results suggest that Tla^a-3-TL antigen expressed in the thymus engages in positive selection of a sizable population of T cells.

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