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CTL by TL Antigen
Expressed in the Thymus
By

From the * Laboratory of Immunology, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya
464, Japan; To elucidate the function of the mouse TL antigen in the thymus, we have derived two TL
transgenic mouse strains by introducing Tlaa-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 Tlaa-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.Tlaa-3-1, Tg.Tlaa-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.Tlaa-3-1 and Tg.Tlaa-3-2, respectively, expressed
TCR
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

, whereas almost all those from C3H expressed TCR
. The MLC from Tg.Tlaa-3-2
and C3H demonstrated high CTL activity against TL, while those from Tg.Tlaa-3-1 had little
or none. The generation of 
CTL recognizing TL in Tg.Tlaa-3-2, but not C3H mice, was
confirmed by the establishment of CTL clones. A total of 14 
CTL clones were established
from Tg.Tlaa-3-2, whereas none were obtained from C3H. Of the 14 
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
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 V
4 chains in 12 of
the 14 clones. Taken together, these results suggest that Tlaa-3-TL antigen expressed in the
thymus engages in positive selection of a sizable population of 
T cells.
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